what is the function of von willebrand factor
binding to other proteins important in platelet adhesion
3047313
multimers are functional. Some cleavage products that result from VWF production are also secreted but probably serve no function. Von Willebrand Factor's primary function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites. It is not an enzyme and, thus, has no catalytic activity. VWF binds to a number of cells and molecules. The most important ones are: VWF plays a major role in blood coagulation. Therefore, VWF deficiency or dysfunction (von Willebrand disease) leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear
Von Willebrand factor
3047313
multimers are functional. Some cleavage products that result from VWF production are also secreted but probably serve no function. Von Willebrand Factor's primary function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites. It is not an enzyme and, thus, has no catalytic activity. VWF binds to a number of cells and molecules. The most important ones are: VWF plays a major role in blood coagulation. Therefore, VWF deficiency or dysfunction (von Willebrand disease) leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear
Von Willebrand factor
1301227
with clinical bleeding. For instance, deficiency of Factor VIII causes classic hemophilia A while deficiencies of Factor IX cause "Christmas disease"(hemophilia B). Antibodies to Factor VIII can also inactivate the Factor VII and precipitate bleeding that is very difficult to control. This is a rare condition that is most likely to occur in older patients and in those with autoimmune diseases. Another common bleeding disorder is Von Willebrand disease. It is caused by a deficiency or abnormal function of the "Von Willebrand" factor, which is involved in platelet activation. Deficiencies in other factors, such as factor XIII or factor VII
Bleeding
3047318
1950s, vWD was shown to be caused by a plasma factor deficiency (instead of being caused by platelet disorders), and, in the 1970s, the VWF protein was purified. von Willebrand Factor has been shown to interact with Collagen, type I, alpha 1. Recently, It has been reported that the cooperation and interactions within the Von Willebrand Factors enhances the adsorption probability in the primary haemostasis. Such cooperation is proven by calculating the adsorption probability of flowing VWF once it crosses another adsorbed one. Such cooperation is held within a wide range of shear rates. Von Willebrand factor von Willebrand Factor
Von Willebrand factor
2091315
other agonists used. A platelet function assay may give an abnormal collagen/epinephrine closure time, and in most cases, a normal collagen/ADP time. Type 2N may be considered if factor VIII levels are disproportionately low, but confirmation requires a "factor VIII binding" assay. Additional laboratory tests that help classify sub-types of vWD include von-willebrand multimer analysis, modified ristocetin induced platelet aggregation assay and vWF propeptide to vWF antigen ratio propeptide. In cases of suspected acquired von-Willebrand syndrome, a mixing study study (analysis of patient plasma along with pooled normal plasma/PNP and a mixture of the two tested immediately, at one hour,
Von Willebrand disease
7309463
Factor from the Weibel-Palade Bodies in the endothelial cells of the vasculature. Because Von Willebrand Factor helps to stabilize circulating levels of factor VIII, the vasopressin analog, Desmopressin can be used to stimulate the AVPR2 receptor and increase levels of circulating factor VIII. This is useful in the treatment of Hemophilia A as well as Von Willebrand disease. In the kidney, AVPR2's primary property is to respond to arginine vasopressin by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of AVPR2 is lost, the disease Nephrogenic Diabetes Insipidus (NDI) results. Vasopressin receptor
Vasopressin receptor 2
6335642
renaming it "constitutional thrombopathy". Numerous papers were subsequently published on the disease and it became eponymously known as von Willebrand disease between the late 1930s and the early 1940s. In 1957, it was discovered that von Willebrand disease is caused by a deficiency of a protein in blood plasma that enables hemostasis. The protein was characterised in 1971, and is known as von Willebrand factor. Von Willebrand factor has two functions. Firstly, it is the carrier molecule for factor VIII, the anti-hemophilic factor. Secondly, it promotes the aggregation of platelets and attachment to the vessel wall. In 2011, Jan van
Erik Adolf von Willebrand
2091321
defective. The ability of the defective von Willebrand factors to coalesce and form large vWF multimers is impaired, resulting in decreased quantity of large vWF multimers and low RCoF activity. Only small multimer units are detected in the circulation. Von Willebrand factor antigen (vWF:Ag) assay is low or normal. This is a "gain of function" defect. The ability of the qualitatively defective vWF to bind to glycoprotein Ib (GPIb) receptor on the platelet membrane is abnormally enhanced, leading to its spontaneous binding to platelets and subsequent rapid clearance of the bound platelets and of the large vWF multimers. Thrombocytopenia may
Von Willebrand disease
16656248
Von Willebrand factor type D domain In molecular biology, the protein domain Von Willebrand factor type D domain belongs to a large family of proteins, named, the von Willebrand factor (vWF). These proteins, the vWF type D domain in particular, is a large, multimeric glycoprotein and it is synthesized by a type of bone marrow cell called megakaryocytes. vWF type D plays 2 important roles in stopping the blood flow or loss of blood. Firstly, it causes platelets to adhere to the inside of the damaged blood vessel walls to prevent leakage of blood. Secondly, it is a carrier protein
Von Willebrand factor type D domain
13828568
Von Willebrand factor type A domain The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders. In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain is found in various plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as
Von Willebrand factor type A domain
16656252
pattern formation, and signal transduction), involving interaction with a large array of ligands. A number of human diseases arise from mutations in VWA domains. Von Willebrand factor type D domain In molecular biology, the protein domain Von Willebrand factor type D domain belongs to a large family of proteins, named, the von Willebrand factor (vWF). These proteins, the vWF type D domain in particular, is a large, multimeric glycoprotein and it is synthesized by a type of bone marrow cell called megakaryocytes. vWF type D plays 2 important roles in stopping the blood flow or loss of blood. Firstly, it
Von Willebrand factor type D domain
13828571
CACNA2D3; CACNA2D4; CFB; CLCA1; CLCA2; CLCA4; COCH; COL12A1; COL14A1; COL20A1; COL21A1; COL22A1; COL28; COL6A1; COL6A2; COL6A3; COL7A1; COLA1L; CaCC1; ITGA1; ITGA10; ITGA11; ITGA2; ITGAD; ITGAE; ITGAL; ITGAM; ITGAX; ITIH1; ITIH2; ITIH3; ITIH4; ITIH5; ITIH5L; LOC285929; LOC340267; LOC389462; LOH11CR2A; MATN1; MATN2; MATN3; MATN4; PARP4; SEL-OB; SVEP1; VIT; VWA1; VWA2; VWF; hCLCA1; hCLCA2; CMG2; Von Willebrand factor type A domain The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders. In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain
Von Willebrand factor type A domain
1684462
to determine which (if any) factor is present as aberrant concentrations. Deficiencies of fibrinogen (quantitative or qualitative) will affect all screening tests. Coagulation defects may cause hemorrhage or thrombosis, and occasionally both, depending on the nature of the defect. Platelet conditions may be congenital or acquired. Some inborn platelet pathologies are Glanzmann's thrombasthenia, Bernard-Soulier syndrome (abnormal glycoprotein Ib-IX-V complex), gray platelet syndrome (deficient alpha granules), and delta storage pool deficiency (deficient dense granules). Most are rare conditions. Most inborn platelet pathologies predispose to hemorrhage. Von Willebrand disease is due to deficiency or abnormal function of von Willebrand factor, and leads
Coagulation
3047311
Von Willebrand factor von Willebrand Factor (VWF) () is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome. Increased plasma levels in a large number of cardiovascular, neoplastic, and connective tissue diseases are presumed to arise from adverse changes to the endothelium, and may contribute to an increased risk of thrombosis. VWF is a large multimeric glycoprotein present in blood plasma and produced constitutively as ultra-large VWF in endothelium (in the Weibel-Palade bodies), megakaryocytes
Von Willebrand factor
16356765
characteristic diseases are the following: Ristocetin-induced platelet aggregation The ristocetin-induced platelet aggregation (RIPA) is an ex vivo assay for live platelet function. It measures platelet aggregation with the help of von Willebrand factor (vWF) and exogenous antibiotic ristocetin added in a graded fashion. It is similar to the ristocetin cofactor assay but has the added benefit in that it helps in the diagnosis of type 2B/pseudo von Willebrand disease (vWD) and Bernard-Soulier syndrome because it uses patient's live endogenous platelets, whereas ristocetin cofactor assay tests the function of only the vWF and not the platelets. Ristocetin cofactor assay uses the
Ristocetin-induced platelet aggregation
16356763
Ristocetin-induced platelet aggregation The ristocetin-induced platelet aggregation (RIPA) is an ex vivo assay for live platelet function. It measures platelet aggregation with the help of von Willebrand factor (vWF) and exogenous antibiotic ristocetin added in a graded fashion. It is similar to the ristocetin cofactor assay but has the added benefit in that it helps in the diagnosis of type 2B/pseudo von Willebrand disease (vWD) and Bernard-Soulier syndrome because it uses patient's live endogenous platelets, whereas ristocetin cofactor assay tests the function of only the vWF and not the platelets. Ristocetin cofactor assay uses the patient's platelet-poor plasma (with vWF
Ristocetin-induced platelet aggregation
2999550
factor to unravel in the same way it would on encountering an injury site. As part of the normal homeostasis of the blood, when von Willebrand factor changes conformation into its active state, it is degraded by its natural catabolic enzyme ADAMTS13, rendering it incapable of binding the collagen at an injury site. As the quantity of von Willebrand factor in the blood decreases, the rate of bleeding dramatically increases. The unraveling of high molecular weight von Willebrand factor in conditions of high shear stress is essential in the prevention of bleeding in the vasculature of the gastrointestinal system where
Heyde's syndrome
3047317
among people that have had ischemic stroke (from blood-clotting) for the first time. Occurrence is not affected by ADAMTS13, and the only significant genetic factor is the person's blood group. High plasma VWF levels were found to be an independent predictor of major bleeding in anticoagulated atrial fibrillation patients. VWF is named after Erik Adolf von Willebrand, a Finnish physician who in 1926 first described a hereditary bleeding disorder in families from the Åland islands. Although Von Willebrand did not identify the definite cause, he distinguished von Willebrand disease (vWD) from hemophilia and other forms of bleeding diathesis. In the
Von Willebrand factor
15114117
(e.g. cell adhesion, migration, homing, pattern formation, and signal transduction), involving interaction with a large array of ligands. A number of human diseases arise from mutations in VWA domains. The domain is named after the von Willebrand factor (VWF) type C repeat which is found in multidomain protein/multifunctional proteins involved in maintaining homeostasis. For the von Willebrand factor the duplicated VWFC domain is thought to participate in oligomerization, but not in the initial dimerization step. The presence of this region in a number of other complex-forming proteins points to the possible involvement of the VWFC domain in complex formation. Von
Von Willebrand factor type C domain
7321519
Ristocetin Ristocetin is an antibiotic, obtained from "Amycolatopsis lurida", previously used to treat staphylococcal infections. It is no longer used clinically because it caused thrombocytopenia and platelet agglutination. It is now used solely to assay those functions "in vitro" in the diagnosis of conditions such as von Willebrand disease (vWD) and Bernard-Soulier syndrome. Platelet agglutination caused by ristocetin can occur only in the presence of von Willebrand factor multimers, so if ristocetin is added to blood lacking the factor (or its receptor—see below), the platelets will not clump. Through an unknown mechanism, the antibiotic ristocetin causes von Willebrand factor to
Ristocetin
2091335
of Von Willebrand's extensive research. In the 1950s, it became clear that a "plasma factor", factor VIII, was decreased in these persons and that Cohn fraction I-0 could correct both the plasma deficiency of FVIII and the prolonged bleeding time. Since this time, the factor causing the long bleeding time was called the "von Willebrand factor" in honor of Erik Adolf von Willebrand. Variant forms of vWF were recognized in the 1970s, and these variations are now recognized as the result of synthesis of an abnormal protein. During the 1980s, molecular and cellular studies distinguished hemophilia A and vWD more
Von Willebrand disease
5708656
ADAMTS13 ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)—also known as "von Willebrand factor-cleaving protease" (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted in blood and degrades large vWf multimers, decreasing their activity. The "ADAMTS13" gene maps to the ninth chromosome (9q34). Since 1982 it had been known that thrombotic thrombocytopenic purpura (TTP), one of the microangiopathic hemolytic anemias (see below), was characterized in its familial form by the presence in plasma of unusually large von Willebrand factor multimers (ULVWF). In 1994,
ADAMTS13
15114116
Von Willebrand factor type C domain Von Willebrand factor, type C (VWFC or VWC)is a protein domain is found in various blood plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins that incorporate vWF domains participate in numerous biological events
Von Willebrand factor type C domain
6335630
Erik Adolf von Willebrand Erik Adolf von Willebrand (1 February 1870 – 12 September 1949) was a Finnish physician who made major contributions to hematology. Von Willebrand disease and von Willebrand factor are named after him. He also researched metabolism, obesity and gout, and was one of the first Finnish physicians to use insulin to treat a diabetic coma. Von Willebrand qualified in medicine in 1896 from the University of Helsinki, where he received his Ph.D in 1899. He worked at the University of Helsinki from 1900 until 1930. From 1908 until his retirement in 1933, he was the head
Erik Adolf von Willebrand
3200303
Weibel–Palade body Weibel–Palade bodies are the storage granules of endothelial cells, the cells that form the inner lining of the blood vessels and heart. They store and release two principal molecules, von Willebrand factor and P-selectin, and thus play a dual role in hemostasis and inflammation. Weibel–Palade bodies were initially described by the Swiss anatomist Ewald R. Weibel and the Romanian physiologist George Emil Palade in 1964. Palade won Nobel Prize in Physiology and Medicine in 1974 for his work on the function of organelles in cells. There are two major components stored within Weibel–Palade bodies. One is von Willebrand
Weibel–Palade body
2999548
Heyde's syndrome Heyde's syndrome is a syndrome of gastrointestinal bleeding from angiodysplasia in the presence of aortic stenosis. It is named after Edward C. Heyde, MD who first noted the association in 1958. It is caused by the induction of Von Willebrand disease type IIA (vWD-2A) by a depletion of Von Willebrand factor (vWF) in blood flowing through the narrowed valvular stenosis. Von Willebrand factor is synthesized in the walls of the blood vessels and circulates freely in the blood in a folded form. When it encounters damage to the wall of a blood vessel, particularly in situations of high
Heyde's syndrome
2999563
confirmed, and the protease responsible, ADAMTS13, was identified. Heyde's syndrome Heyde's syndrome is a syndrome of gastrointestinal bleeding from angiodysplasia in the presence of aortic stenosis. It is named after Edward C. Heyde, MD who first noted the association in 1958. It is caused by the induction of Von Willebrand disease type IIA (vWD-2A) by a depletion of Von Willebrand factor (vWF) in blood flowing through the narrowed valvular stenosis. Von Willebrand factor is synthesized in the walls of the blood vessels and circulates freely in the blood in a folded form. When it encounters damage to the wall of
Heyde's syndrome
2999562
in the narrowed stenotic aortic valve and thus cleared from circulation at a much higher rate than in healthy individuals. This hypothesis received strong support in 2003 by the publication of a report by Vincentelli et al. that demonstrated a strong association between von Willebrand factor defects and the severity of aortic valve stenosis. They also showed these defects resolved within hours following aortic valve replacement surgery and remained resolved in most people, although in some people the von Willebrand factor defects had returned at six months. Following this observation the shear stress dependent depletion of von Willebrand factor was
Heyde's syndrome
3047314
in narrow vessels. From studies it appears that VWF uncoils under these circumstances, decelerating passing platelets. Recent research also suggests that von Willebrand Factor is involved in the formation of blood vessels themselves, which would explain why some people with von Willebrand disease develop vascular malformations (predominantly in the digestive tract) that can bleed excessively. The biological breakdown (catabolism) of VWF is largely mediated by the enzyme ADAMTS13 (acronym of ""a" "d"isintegrin-like "a"nd "m"etalloprotease with "t"hrombo"s"pondin type 1 motif no. "13""). It is a metalloproteinase that cleaves VWF between tyrosine at position 842 and methionine at position 843 (or 1605–1606
Von Willebrand factor
2858035
Factor VIII Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the "F8" gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation disorder. Factor VIII is produced in liver sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein
Factor VIII
2091308
Von Willebrand disease Von Willebrand disease (vWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion. As well as humans, it is known to affect several breeds of dogs. The three forms of vWD are: hereditary, acquired, and pseudo or platelet type. The three types of hereditary vWD are: vWD type 1, vWD type 2, and vWD type 3. Type 2 contains various subtypes. Platelet type
Von Willebrand disease
6335631
of the department of medicine at the Deaconess Hospital in Helsinki, where he also was physician-in-chief from 1922 to 1931. In 1924, Von Willebrand was consulted about a young girl with a bleeding disorder. He described this disorder in 1926, distinguishing it from hemophilia. The disorder was named after him, becoming known as von Willebrand disease. The cause of the disease was later discovered to be a deficiency of a protein, now known as von Willebrand factor, that enables hemostasis. Von Willebrand was born on 1 February 1870 in Vaasa, then part of the Grand Duchy of Finland in the
Erik Adolf von Willebrand
16656249
for factor VIII (FVIII) which helps blood to clot. One of the functions of von Willebrand factor (vWF) is to serve as a carrier of clotting factor VIII (FVIII). The native conformation of the D' domain of vWF is not only required for factor VIII (FVIII) binding but also for normal multimerisation and optimal secretion. The interaction between blood clotting factor VIII and VWF is necessary for normal survival of blood clotting factor VIII in blood circulation. The VWFD domain is a highly structured region, in which the first conserved Cys has been found to form a disulphide bridge with
Von Willebrand factor type D domain
1622268
haemophilia A, due to differences in changes to the factor VIII gene (and the resulting protein). Individuals with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having "severe haemophilia", those with 1–5% active factor have "moderate haemophilia", and those with "mild haemophilia" have between 5–40% of normal levels of active clotting factor. Two of the most common differential diagnoses are haemophilia B which is a deficiency in Factor IX and von Willebrand Disease which is a deficiency in von Willebrand factor (needed for the proper functioning of Factor VIII);
Haemophilia A
2999561
and acquired von Willebrand's disease type IIA, which is corrected by surgical replacement of the aortic valve. They also noted that von Willebrand's disease is known to cause bleeding from angiodysplasia. Based on these facts, they hypothesized that acquired von Willebrand's disease is the true culprit behind gastrointestinal bleeding in aortic stenosis. They also proposed a possible mechanism for the acquired von Willebrand's disease, noting that von Willebrand factor is most active in 'high shear' vessels (meaning small vessels in which blood flows rapidly). They used this fact to hypothesize that this may mean that von Willebrand factor is activated
Heyde's syndrome
2999549
velocity blood flow, it binds to the collagen beneath the damaged endothelium and uncoils into its active form. Platelets are attracted to this activated form of von Willebrand factor and they accumulate and block the damaged area, preventing bleeding (see von Willebrand factor). In people with aortic valve stenosis, the stenotic aortic valve becomes increasingly narrowed resulting in an increase in speed of the blood through the valve in order to maintain cardiac output. This combination of a narrow opening and a higher flow rate results in an increased shear stress on the blood. This higher stress causes von Willebrand
Heyde's syndrome
1596481
aortic valve is not replaced. CHF in the setting of AS is due to a combination of left ventricular hypertrophy with fibrosis, systolic dysfunction (a decrease in the ejection fraction) and diastolic dysfunction (elevated filling pressure of the LV). In Heyde's syndrome, aortic stenosis is associated with gastrointestinal bleeding due to angiodysplasia of the colon. Recent research has shown that the stenosis causes a form of von Willebrand disease by breaking down its associated coagulation factor (factor VIII-associated antigen, also called von Willebrand factor), due to increased turbulence around the stenotic valve. Notwithstanding the foregoing, the American Heart Association has
Aortic stenosis
2091324
as having hemophilia A. Type 3 is the most severe form of vWD (homozygous for the defective gene) and is characterized by complete absence of production of vWF. The von Willebrand factor is undetectable in the vWF antigen assay. Since the vWF protects coagulation factor VIII from proteolytic degradation, total absence of vWF leads to extremely low factor VIII level, equivalent to that seen in severe hemophilia A with its clinical manifestations of life-threatening external and internal hemorrhages. The inheritance pattern of vWD type 3 is autosomal recessive, while the inheritance pattern of hemophilia A is X-linked recessive. Platelet-type vWD
Von Willebrand disease
11664923
PFA-100 The PFA-100 (Platelet Function Assay or Platelet Function Analyser) is a platelet function analyser that aspirates blood in vitro from a blood specimen into disposable test cartridges through a microscopic aperture cut into a biologically active membrane at the end of a capillary. The membrane of the cartridges are coated with collagen and adenosine diphosphate (ADP) or collagen and epinephrine inducing a platelet plug to form which closes the aperture. The PFA test result is dependent on platelet function, plasma von Willebrand Factor level, platelet number, and (to some extent) the hematocrit. The PFA test is initially performed with
PFA-100
7321522
the ristocetin cofactor activity depends only upon high-molecular multimers of the factor present in circulating plasma. Ristocetin Ristocetin is an antibiotic, obtained from "Amycolatopsis lurida", previously used to treat staphylococcal infections. It is no longer used clinically because it caused thrombocytopenia and platelet agglutination. It is now used solely to assay those functions "in vitro" in the diagnosis of conditions such as von Willebrand disease (vWD) and Bernard-Soulier syndrome. Platelet agglutination caused by ristocetin can occur only in the presence of von Willebrand factor multimers, so if ristocetin is added to blood lacking the factor (or its receptor—see below), the
Ristocetin
3825741
von Willebrand Factor, and Factor VIII-von Willebrand Factor complex. OPG has been identified as having a role in tumour growth and metastasis, heart disease, immune system development and signalling, mental health, diabetes, and the prevention of pre-eclampsia and osteoporosis during pregnancy. OPG is largely expressed by osteoblast lineage cells of bone, epithelial cells of the gastrointestinal tract, lung, breast and skin, vascular endothelial cells, as well as B-cells and dendritic cells in the immune system. OPG is a soluble glycoprotein which can be found as either a 60-kDa monomer or a 120-kDa dimer linked by disulfide bonds. The dimerisation of
Osteoprotegerin
2091309
vWD is also an inherited condition. In 2008 a new diagnostic category of "Low VWF" was proposed to include those individuals whose Von Willebrand Factor levels were below the normal reference range but not low enough to be Von Willebrand Disease (levels in the 30-50 IU/dL range). Patients with Low VWF can experience bleeding, despite mild reductions in VWF levels. vWD type 1 is the most common type of the disorder, with mild bleeding symptoms such as nosebleeds and occasionally more severe symptoms can occur. Blood type can affect the presentation and severity of symptoms of vWD. vWD type 2
Von Willebrand disease
3396303
wet nights per week and are 4.5 times more likely to sleep without disruption compared with placebo. Desmopressin has some benefit in adults who have problems with night time urination (known as nocturia). The FDA approved this use for those who make excess urine in 2017. Desmopressin (DDAVP) stimulates the release of von Willebrand factor (vWF) from the Weibel–Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) 3 to 5-fold. Desmopressin can be used to promote the release of von Willebrand factor (with subsequent increase in factor VIII survival secondary to vWF
Desmopressin
6549817
PGE-M down and remain present at high concentrations. Apart from elevated PGE levels, studies in patients with hypertrophic osteoarthropathy also showed increased plasma levels of several other mediators, such as Von Willebrand factor and vascular endothelial growth factor (VEGF). These substances could also have a role in PDP progression and proliferation. In contrast to HPGD mutations, suspected mutations for these factors have not been reported yet. Von Willebrand factor is a marker of platelet and endothelial activation. This suggests that the activation of endothelial cells and platelets play an important role in the pathogenesis of PDP. VEGF promotes angiogenesis (growth
Primary hypertrophic osteoathropathy
1684464
C (factor XI deficiency, mild bleeding tendency). Hemophilia A and B are X-linked recessive disorders, whereas Hemophilia C is a much more rare autosomal recessive disorder most commonly seen in Ashkenazi Jews. Von Willebrand disease (which behaves more like a platelet disorder except in severe cases), is the most common hereditary bleeding disorder and is characterized as being inherited autosomal recessive or dominant. In this disease, there is a defect in von Willebrand factor (vWF), which mediates the binding of glycoprotein Ib (GPIb) to collagen. This binding helps mediate the activation of platelets and formation of primary hemostasis. Bernard-Soulier syndrome
Coagulation
4104985
Medicinally it is used as an antithrombotic (antiplatelet), to reduce blood viscosity, and as a volume expander in hypovolaemia. Dextran 70 is on the WHO Model List of Essential Medicines, the most important medications needed in a health system. These agents are used commonly by microsurgeons to decrease vascular thrombosis. The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium, increasing their electronegativity and thus reducing erythrocyte aggregation and platelet adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor, thereby decreasing platelet function. Clots formed after administration of dextrans are more easily lysed due
Dextran
2999551
small arterioles are common, as platelets cannot bind to damaged blood vessel walls well in such conditions. This is particularly true in the presence of intestinal angiodysplasia, where arteriovenous malformations lead to very high blood flow, and so the loss of von Willebrand factor can lead to much more extensive bleeding from these lesions. When people with aortic stenosis also have gastrointestinal bleeding, it is invariably from angiodysplasia. It has been hypothesized that defects in high molecular weight von Willebrand factor could actually be the cause of the arteriovenus malformations in intestinal angiodysplasia, rather than just making existing angiodysplasic lesions
Heyde's syndrome
3458626
αβ, formerly known as glycoprotein IIb/IIIa (GpIIb/IIIa), which is an integrin aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine, collagen, or thrombin. GpIIb/IIIa is essential to blood coagulation since the activated receptor has the ability to bind fibrinogen (as well as von Willebrand factor, fibronectin, and vitronectin), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation). In contrast, glycoproteinIb receptors are normal with Glanzmann's thrombasthenia. The role of GpIb is to enable platelet activation by contact with the von Willebrand factor-collagen complex that is exposed when the endothelial blood vessel lining is damaged.
Glanzmann's thrombasthenia
12382487
VWA2 von Willebrand factor A domain-containing protein 2, also known as A domain-containing protein similar to matrilin and collagen (AMACO) is a protein that in humans is encoded by the "VWA2" gene. AMACO is a member of the von Willebrand factor A-like (VWA) domain containing protein superfamily and consists of three VWA-like domains, two EGF-like domains, a cysteine-rich domain and a unique C-terminal domain. AMACO is an extracellular matrix protein and mostly deposited adjacent to basement membranes. AMACO binds directly to FRAS1 which is part of the Fraser complex important for epithelial-connective tissue interaction, the exact biological role of AMACO,
VWA2
12382488
however, is still unknown. In 2005 AMACO was found markedly induced in colon cancers ; indicating that it might be a good candidate as a biomarker for this type of cancer. VWA2 von Willebrand factor A domain-containing protein 2, also known as A domain-containing protein similar to matrilin and collagen (AMACO) is a protein that in humans is encoded by the "VWA2" gene. AMACO is a member of the von Willebrand factor A-like (VWA) domain containing protein superfamily and consists of three VWA-like domains, two EGF-like domains, a cysteine-rich domain and a unique C-terminal domain. AMACO is an extracellular matrix
VWA2
17427833
bleeding episodes or in preventing postoperative hemorrhage when given prior to minor surgical operations in patients with mild to moderate hemophilia or some types of von Willebrand disease. Lusher introduced the hemostatic use of desmopressin to the United States. After first trying it on herself and her colleagues, and documenting the rise of factor VIII levels, she proceeded to use it in patients with hemophilia and von Willebrand disease, and reported its efficacy. Desmopressin was finally approved for use in hemophilia and von Willebrand disease by the FDA in 1984. In the 1980s, Lusher and her colleagues recognized an immune
Jeanne Lusher
2091316
and at two hours) should be performed. Detection of vWD is complicated by vWF being an acute phase reactant with levels rising in infection, pregnancy, and stress. Other tests performed in any patient with bleeding problems are a complete blood count-CBC (especially platelet counts), activated partial thromboplastin time-APTT, prothrombin time with International Normalized Ratio-PTINR, thrombin time-TT, and fibrinogen level. Testing for factor IX may also be performed if hemophilia B is suspected. Other coagulation factor assays may be performed depending on the results of a coagulation screen. Patients with von Willebrand disease typically display a normal prothrombin time and a
Von Willebrand disease
12106828
Timothy A. Springer Timothy "Tim" A. Springer, Ph.D. is an immunologist and Latham Family Professor at Harvard Medical School. Springer is best known for his pioneering work in discovering the first integrins and intercellular adhesion molecules (ICAMs) and elucidating how these cell adhesion molecules function in the immune system. His innovative use of monoclonal antibodies in his research paved the way for the development of therapeutic antibodies, known as selective adhesion molecule inhibitors, to treat autoimmune diseases. In recent years, Springer's research interest has expanded to include malaria, transforming growth factor beta (TGF-β) signaling molecules, and von Willebrand factor. Springer
Timothy A. Springer
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the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus. Desmopressin is a synthetic analog of the natural antidiuretic hormone vasopressin. Its overuse can lead to water retention and dilutional hyponatremia with consequent convulsion. For patients with vWD scheduled for surgery and cases of vWD disease complicated by clinically significant hemorrhage, human-derived medium purity factor VIII concentrates, which also contain von Willebrand factors, are available for prophylaxis and treatment. Humate P, Alphanate, Wilate and Koate HP are commercially available for prophylaxis and treatment of vWD. Monoclonally purified factor VIII
Von Willebrand disease
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failure and changes in the level of consciousness. Treatment of TTP was revolutionized in the 1980s with the application of plasmapheresis. According to the Furlan-Tsai hypothesis, this treatment works by removing antibodies against the von Willebrand factor-cleaving protease ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease proteins to the patient, restoring a normal level of von Willebrand factor multimers. Patients with persistent antibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to explain how plasmapheresis treats TTP. Many cases of ITP can be left untreated, and spontaneous remission (especially in children) is not
Thrombocytopenia
16656250
the second conserved one. The D8 domain (amino acids 6-102) is a highly structured region containing 24 paired cysteine residues. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of alpha-helices and beta-strands. A family of growth regulators, all belong to genes being expressed after being induced or stimulated by growth factors or oncogenes. Sequence analysis of this family revealed the presence of four distinct modules. Each module has homologues in other extracellular mosaic proteins such as Von Willebrand factor, slit, thrombospondins, fibrillar collagens, IGF-binding proteins and mucins. Classification and analysis of these modules suggests
Von Willebrand factor type D domain
10103832
of the central nervous system in the modulation of side-to-side and side-to-substratum interactions, and also in promoting neurite outgrowth. The identification of conserved domains including Emilin (EMI), von Willebrand factor D (vWD) low-density lipoprotein receptor type A repeats (LDLrA) domains, SCO repeats (SCORs), 26 thrombospondin type 1 repeats (TSRs), a coagulation factor 5/8 type C (FA5-8C) or discoidin motif and a C-terminal cystin knot (CTCK) domain provides a wider insight into the putative function of this protein. Similar types of arrangement was encountered in zonadhesins and immunoglobulin G (IgG) FC binding fragment which may account for SCO-spondin functional aspect on
Subcommissural organ
2324623
also prone to von Willebrand disease (vWD). vWD in dogs is an inherited bleeding disorder that occurs due to qualitative or quantitative deficiency of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion. Schnauzers have a specific groom cut that is standard among the schnauzer breeds. Schnauzers require regular grooming, either by stripping (mostly seen in show dogs), or by clipping (a short-cut usually reserved for family pets). Stripping removes the loose, dead coat; it may be done by hand, called finger stripping, or plucking, or with a stripping knife; either way, it is a laborious
Miniature Schnauzer
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by other coagulation factors such as haemophilia. Diseases that cause prolonged bleeding time include thrombocytopenia, disseminated intravascular coagulation (DIC), Bernard-Soulier disease, and Glanzmann's thrombasthenia. Aspirin and other cyclooxygenase inhibitors can significantly prolong bleeding time. While warfarin and heparin have their major effects on coagulation factors, an increased bleeding time is sometimes seen with use of these medications as well. People with von Willebrand disease usually experience increased bleeding time, as von Willebrand factor is a platelet adhesion protein, but this is not considered an effective diagnostic test for this condition. It is also prolonged in hypofibrinogenemia. In the British comedy
Bleeding time
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Willebrand factor (vWF) and fibrinogen will act as anchors to allow platelets to adhere onto the vessel wall. These molecules are released from the platelet themselves as a result of degranulation, a physiological change in the platelet's shape due to the secretion of the contents of the dense granules and alpha granules. From the dense granules, serotonin and adenosine triphosphate are released. From the alpha granules come molecules such as the platelet-derived growth factor, fibrinogen, and the von Willebrand factor (vWF), a glycoprotein critical in platelet activation and adhesion. The ADP secreted from the dense granules then binds to receptors
Platelet plug
2091311
It has 52 exons spanning 178kbp. Types 1 and 2 are inherited as autosomal dominant traits. Occasionally, type 2 also inherits recessively. Type 3 is inherited as autosomal recessive. However, some individuals heterozygous for type 3 may be diagnosed of vWD type 1, indicating an intermediate inheritance in that cases. vWD occurs in approximately 1% of the population and affects men and women equally. Von Willebrand factor is mainly active in conditions of high blood flow and shear stress. Deficiency of vWF, therefore, shows primarily in organs with extensive small vessels, such as skin, gastrointestinal tract, and uterus. In angiodysplasia,
Von Willebrand disease
2999554
electrophoresis; in people with vWD-2A, the large molecular weight von Willebrand factors will be absent from the SDS-agarose electrophoresis plate. The definitive treatment for Heyde's syndrome is surgical replacement of the aortic valve. Recently, it has been proposed that transcatheter aortic valve implantation (TAVI) can also be used for definitive management. Direct surgical treatment of the bleeding (e.g. surgical resection of the bleeding portion of the bowel) is only rarely effective. Medical management of symptoms is possible also, although by necessity temporary, as definitive surgical management is required to bring levels of von Willebrand factor back to normal. In severe
Heyde's syndrome
3200308
importance of Weibel–Palade bodies are highlighted by some human disease mutations. Mutations within vWF are the usual cause of the most common inherited bleeding disorder, von Willebrand disease. VWD has an estimated prevalence in some human populations of up to 1%, and is most often characterized by prolonged and variable mucocutaneous bleeding. Type III von Willebrand Disease is a severe bleeding disorder, like severe hemophilia type A or B. VWF acts in primary hemostasis to recruit platelets at a site of injury, and is also important in secondary hemostasis, acting as a chaperone for coagulation factor VIII (FVIII). Weibel–Palade body
Weibel–Palade body
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of the gene) in the A2 domain. This breaks down the multimers into smaller units, which are degraded by other peptidases. Hereditary or acquired defects of VWF lead to von Willebrand disease (vWD), a bleeding diathesis of the skin and mucous membranes, causing nosebleeds, menorrhagia, and gastrointestinal bleeding. The point at which the mutation occurs determines the severity of the bleeding diathesis. There are three types (I, II and III), and type II is further divided in several subtypes. Treatment depends on the nature of the abnormality and the severity of the symptoms. Most cases of vWD are hereditary, but
Von Willebrand factor
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(α-granules of platelets), and subendothelial connective tissue. The basic VWF monomer is a 2050-amino acid protein. Every monomer contains a number of specific domains with a specific function; elements of note are: Monomers are subsequently N-glycosylated, arranged into dimers in the endoplasmic reticulum and into multimers in the Golgi apparatus by crosslinking of cysteine residues via disulfide bonds. With respect to the glycosylation, VWF is one of only a few proteins that carry ABO blood group system antigens. Multimers of VWF can be extremely large, >20,000 kDa, and consist of over 80 subunits of 250 kDa each. Only the large
Von Willebrand factor
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Platelet membrane glycoprotein Platelet membrane glycoproteins are surface glycoproteins found on platelets (thrombocytes) which play a key role in hemostasis. When the blood vessel wall is damaged, platelet membrane glycoproteins interact with the extracellular matrix. Membrane glycoproteins GPIa/IIa, GPVI and probably GPIV as well, function as receptors engaged in platelet adhesion to collagen. The leading role in the elimination of high-stress injury is taken by the GPIb-IX-V complex. The binding of von Willebrand factor (vWF) results in conformational changes within the GPIb-V-IX complex. In consequence, this complex activates GPIIb / IIIa membrane glycoproteins allowing them to bind fibrinogen. Fibrinogen molecules
Platelet membrane glycoprotein
2340758
muscle to relax in order to regulate the amount of tone in blood vessels. However, dysfunction within these Ca-activated pathways can lead to an increase in tone caused by unregulated smooth muscle contraction. This type of dysfunction can be seen in cardiovascular diseases, hypertension, and diabetes. Calcium coordination plays an important role in defining the structure and function of proteins. An example a protein with calcium coordination is von Willebrand factor (vWF) which has an essential role in blood clot formation process. It was discovered using single molecule optical tweezers measurement that calcium-bound vWF acts as a shear force sensor
Calcium in biology
1993853
and others. His most important discovery was made while using an experimental strategy known as a pulse-chase analysis. In the experiment Palade and his colleagues were able to confirm an existing hypothesis that a secretory pathway exists and that the Rough ER and the Golgi apparatus function together. He focused on Weibel-Palade bodies (a storage organelle unique to the endothelium, containing von Willebrand factor and various proteins) which he described together with the Swiss anatomist Ewald R. Weibel. The following is a concise excerpt from Palade's Autobiography appearing in the Nobel Award documents One notes also that the Nobel Prize
George Emil Palade
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plasma-derived molecule. It can not prevent hemorrhagic bleeding associated with von Willebrand's disease since it is not a von Willebrand factor. Moroctocog alfa Moroctocog alfa (trade name ReFacto) is a recombinant antihemophilic factor genetically engineered from Chinese hamster ovary (CHO) cell line. Chemically it is a glycoprotein. It is manufactured by Genetics Institute, Inc. and used to control and prevent hemorrhagic bleeding and prophylaxis associated with surgery or to reduce the number of spontaneous bleeding episodes in patients with hemophilia A. It is partially a recombinant coagulation factor VIII since it has an amino acid sequence which compares to the
Moroctocog alfa
2999555
bleeding, blood transfusions and IV fluid infusions can be used to maintain blood pressure. In addition, desmopressin (DDAVP) is known to be effective in people with von Willebrand's disease, including people with valvular heart disease. Desmopressin stimulates release of von Willebrand factor from blood vessel endothelial cells by acting on the V2 receptor, which leads to decreased breakdown of Factor VIII. Desmopressin is thus sometimes used directly to treat mild to moderate acquired von Willebrand's disease and is an effective prophylactic agent for the reduction of bleeding during heart valve replacement surgery. The exact prevalence of the syndrome is unknown,
Heyde's syndrome
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tissues. In the same year, Jorpes and the surgeon Clarence Crafoord used heparin to prevent postoperative thrombosis. Crafoord later confirmed the usefulness of heparin in treating thrombosis. Jorpes' classic study on the use of heparin in the treatment of thrombosis was published in 1946. Since the 1940s, Jorpes participated in studies on fibrinogen, factor VIII, plasminogen, prothrombin and thrombin. He also worked on von Willebrand disease with Erik Adolf von Willebrand. In 1961, Jorpes and the docent Viktor Mutt isolated the hormone secretin. Jorpes was known as a strong personality. There was often tensions between Jorpes and his students and
Erik Jorpes
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a stable noncovalent complex with von Willebrand factor. Upon activation by thrombin (factor IIa), it dissociates from the complex to interact with factor IXa in the coagulation cascade. It is a cofactor to factor IXa in the activation of factor X, which, in turn, with its cofactor factor Va, activates more thrombin. Thrombin cleaves fibrinogen into fibrin which polymerizes and crosslinks (using factor XIII) into a blood clot. No longer protected by vWF, activated FVIII is proteolytically inactivated in the process (most prominently by activated protein C and factor IXa) and quickly cleared from the blood stream. Factor VIII is
Factor VIII
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disorder that affected the Swedish-speaking minority. After his retirement in 1933 he became an avid gardener and a supporter of nature conservation. Von Willebrand died on 12 September 1949, at the age of 79. In 1994, he was commemorated with a stamp issued by the Åland Islands. The stamp was one in a set of two: the other commemorated Erik Jorpes, known for his pioneering work on heparin. The following list of publications is compiled from Lassila, R.; Lindberg, O. (2013). "Erik von Willebrand". "Haemophilia". 19 (5): 645. Erik Adolf von Willebrand Erik Adolf von Willebrand (1 February 1870 –
Erik Adolf von Willebrand
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(sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot. Factor VIII participates in blood coagulation; it is a cofactor for factor IXa which, in the presence of Ca and phospholipids, forms a complex that converts factor X to the activated form Xa. The factor VIII gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events.
Factor VIII
4464849
larger numbers of circulating microvesicles (fragments of damaged cells) that bear tissue factor. Platelet aggregation may be increased, and there are higher levels of coagulation proteins such as von Willebrand factor, fibrinogen, factor VII and factor VIII. Obesity also increases the risk of recurrence after an initial episode of thrombosis. A number of conditions that have been linked with venous thrombosis are possibly genetic and possibly acquired. These include: elevated levels of factor VIII, factor IX, factor XI, fibrinogen and thrombin-activatable fibrinolysis inhibitor, and decreased levels of tissue factor pathway inhibitor. Activated protein C resistance that is not attributable to
Thrombophilia
6899056
These mutations do not allow GPIb-IX-V complex to bind to the von Willebrand factor, which in turn is what would help platelets adhere to a site of injury which eventually helps stop bleeding. In terms of diagnosis Bernard–Soulier syndrome is characterized by prolonged bleeding time, thrombocytopenia, increased megakaryocytes, and enlarged platelets, Bernard–Soulier syndrome is associated with quantitative or qualitative defects of the platelet glycoprotein complex GPIb/V/IX. The degree of thrombocytopenia may be estimated incorrectly, due to the possibility that when the platelet count is performed with automatic counters, giant platelets may reach the size of red blood cells. The large
Bernard–Soulier syndrome
2910203
by about 10 times. Factor V Leiden, which makes factor V resistant to inactivation by activated protein C, and the genetic variant prothrombin G20210A, which causes increased prothrombin levels, are predominantly expressed in Caucasians. They moderately increase risk for VTE, by three to eight times for factor V Leiden and two to three times for prothrombin G20210A. Having a non-O blood type roughly doubles VTE risk. Non-O blood type is common in all races, making it an important risk factor. Individuals without O blood type have higher blood levels of von Willebrand factor and factor VIII than those with O
Deep vein thrombosis
3962809
dilution) with normal plasma. If the abnormality does not disappear, the sample is said to contain an "inhibitor" (either heparin, antiphospholipid antibodies or coagulation factor specific inhibitors), while if it does disappear a factor deficiency is more likely. Deficiencies of factors VIII, IX, XI and XII and rarely von Willebrand factor (if causing a low factor VIII level) may lead to a prolonged aPTT correcting on mixing studies. The aPTT was first described in 1953 by researchers at the University of North Carolina at Chapel Hill explaining the Carolina blue Vacutainer tube top color. Partial thromboplastin time The partial thromboplastin
Partial thromboplastin time
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platelet agglutination (RIPA) assays. Factor VIII levels are also performed because factor VIII is bound to vWF which protects the factor VIII from rapid breakdown within the blood. Deficiency of vWF can then lead to a reduction in factor VIII levels, which explains the elevation in PTT. Normal levels do not exclude all forms of vWD, particularly type 2, which may only be revealed by investigating platelet interaction with subendothelium under flow, a highly specialized coagulation study not routinely performed in most medical laboratories. A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the
Von Willebrand disease
8898331
Platelet alpha-granule Alpha granules (or α-granules) are a cellular component of platelets. Platelets contain different types of granules that perform different functions including alpha granules, dense granules, and lysosomes. Of these alpha granules are the most common. The term "alpha granules" is used to describe granules containing several growth factors. Contents include insulin-like growth factor 1, platelet-derived growth factors, TGFβ, platelet factor 4 (which is a heparin-binding chemokine) and other clotting proteins (such as thrombospondin, fibronectin, factor V, and von Willebrand factor). The alpha granules express the adhesion molecule P-selectin and CD63. These are transferred to the membrane after synthesis.
Platelet alpha-granule
13989646
when plasma exchange is indicated. Cryosupernatant The term cryosupernatant (also called cryo-poor plasma, cryoprecipitate depleted, cryoprecipitate reduced plasma) refers to plasma from which the cryoprecipitate has been removed. The resulting plasma has reduced levels of factor VIII (FVIII), von Willebrand factor (VWF), factor XIII (FXIII), fibronectin and fibrinogen. While the levels of FVIII are greatly reduced, levels of fibrinogen can be as much as 70% of original levels. Cryosupernatant plasma can be used when replacement of FVIII is not required, and is indicated for plasma exchange for patients with thrombotic thrombocytopenic purpura (TTP) as well as for treatment of hemolytic-uremic
Cryosupernatant
13989645
Cryosupernatant The term cryosupernatant (also called cryo-poor plasma, cryoprecipitate depleted, cryoprecipitate reduced plasma) refers to plasma from which the cryoprecipitate has been removed. The resulting plasma has reduced levels of factor VIII (FVIII), von Willebrand factor (VWF), factor XIII (FXIII), fibronectin and fibrinogen. While the levels of FVIII are greatly reduced, levels of fibrinogen can be as much as 70% of original levels. Cryosupernatant plasma can be used when replacement of FVIII is not required, and is indicated for plasma exchange for patients with thrombotic thrombocytopenic purpura (TTP) as well as for treatment of hemolytic-uremic syndrome (HUS) by plasma exchange,
Cryosupernatant
14545948
in pregnancy likely evolved to protect women from hemorrhage at the time of miscarriage or childbirth. In third world countries, the leading cause of maternal death is still hemorrhage. In the United States 2011-2013, hemorrhage made up of 11.4% and pulmonary embolisms made up of 9.2% of all pregnancy-related deaths. The increase risk of clots can be attributed to several things. Plasma levels of pro-coagulantion factors increased markedly in pregnancy, including: von Willebrand Factor, fibrinogen, factor VII, factor VIII, and factor X. Both the production of prostacyclin (an inhibitor of platelet aggregation) and thromboxane (an inducer of platelet aggregation and
Maternal physiological changes in pregnancy
6187802
factors and are suitable for patients in whom FFP is indicated. Single-donor plasma is efficacious in the treatment of mild deficiencies of stable clotting factors. It also is of value in treatment of multiple deficiencies as in reversal of warfarin effects or in liver disease. Safe and effective alternative treatment often exists so that FFP is no longer the therapy of choice in many conditions. Cryoprecipitate should be used when fibrinogen or von Willebrand factor is needed. For treatment of hemophilia A, cryoprecipitate or factor VIII concentrates, heated or unheated, are available. For treatment of severe hemophilia B, factor IX
Fresh frozen plasma
1623239
for hemophilia B can be done via the following tests/methods: The differential diagnosis for this inherited condition is the following: hemophilia A, factor XI deficiency, von Willebrand disease, fibrinogen disorders and Bernard-Soulier syndrome Treatment is given intermittently, when there is significant bleeding. It includes intravenous infusion of factor IX and/or blood transfusions. NSAIDS should be avoided once the diagnosis is made since they can exacerbate a bleeding episode. Any surgical procedure should be done with concomitant tranexamic acid. In the 1950s and 1960s, with newfound technology and gradual advances in medicine, pharmaceutical scientists found a way to take the factor
Haemophilia B
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sequester APA, and therefore declining tolerance to the presence of anthrax bacteria. There is the potential that other memory B-Cell populations will be adversely affected as well. Furin is the protein activator for pro-parathyroid hormone, transforming growth factor beta 1, von Willebrand factor, pro-albumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, gonadotropin, and nerve growth factor. Furin is also essential to maintain peripheral immune tolerance by creating memory T-cells and suppressor T-cells. Based on a retrospective cohort study of female military members inoculated during pregnancy, there may be a small risk of birth defect for inoculation during first trimester. However, the difference
Anthrax vaccine adsorbed
1610280
platelet factor 4 (PF4), connecting innate and adaptive immune responses. "Spontaneous and excessive bleeding" can occur because of platelet disorders. This bleeding can be caused by deficient numbers of platelets, dysfunctional platelets, or very excessive numbers of platelets: over 1.0 million/microliter. (The excessive numbers create a relative von Willebrand factor deficiency due to sequestration.) One can get a clue as to whether bleeding is due to a platelet disorder or a coagulation factor disorder by the characteristics and location of the bleeding. All of the following suggest platelet bleeding, not coagulation bleeding: the bleeding from a skin cut such as
Platelet
6335637
batch of the hormone ever delivered to Finland. Von Willebrand remained at the University of Helsinki until 1930. He was physician-in-chief of the Deaconess Hospital from 1922 to 1931, and became honorary professor in 1930. He remained head of the Deaconess Hospital's department of medicine until his retirement in 1933. Von Willebrand continued to publish articles after his retirement. On his 75th birthday, he released his last paper, entitled "En genetisk blodsykdom blant innbyggerne på Åland" ("A genetic blood disease amongst the islanders of Åland"). In April 1924, Von Willebrand was consulted about a 5-year-old girl named Hjördis Sundblom with
Erik Adolf von Willebrand
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Russian Empire. He was the third child of Fredrik Magnus von Willebrand and Signe Estlander. Fredrik had received a military education and later became an engineer. Von Willebrand belonged to a German noble family; his ancestors settled in Finland in the 18th century. Von Willebrand attended Vaasa Lyceum, where he excelled in botany, chemistry and zoology. During this time, he spent his summers collecting botanical, lepidopterological and ornithological specimens, and his winters exploring the Gulf of Bothnia. After obtaining his baccalaureate in 1890, he began his studies at the University of Helsinki, then referred to as the Imperial Alexander University
Erik Adolf von Willebrand
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longer duration of treatment with continuous therapy is also more protective. The increase in risk of endometrial cancer is similarly decreased with continuous estrogen–progestogen therapy ( = 0.2–0.7). For these reasons, progestogens are always used alongside estrogens in women who have intact uteruses. Estrogens affect liver protein synthesis and thereby influence the cardiovascular system. They have been found to affect the production of a variety of coagulation and fibrinolytic factors, including increased factor IX, von Willebrand factor, thrombin–antithrombin complex (TAT), fragment 1+2, and D-dimer and decreased fibrinogen, factor VII, antithrombin, protein S, protein C, tissue plasminogen activator (t-PA), and plasminogen
Estrogen (medication)
7781773
proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a calcium-dependent serine endoprotease that can efficiently cleave precursor proteins at their paired basic amino acid processing sites. Some of its substrates are: proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. A furin-like pro-protein convertase has been implicated in the processing of RGMc (also called hemojuvelin), a gene involved in a severe iron-overload disorder called juvenile hemochromatosis. Both the
Furin
3396304
complexing) in patients with coagulation disorders such as von Willebrand disease, mild hemophilia A (factor VIII deficiency), and thrombocytopenia. It can be used with uremic induced platelet dysfunction. It is not effective in the treatment of hemophilia B (factor IX deficiency) or severe hemophilia A. The usefulness of desmopressin in hemophilia A depends predominantly on whether the deficiency involved is qualitative (i.e., there is a functional mutation of the protein itself) or quantitative (i.e., there is decreased production of a functionally normal protein). Desmopressin is most effective in patients with quantitative deficiencies, because by increasing the release of vWF, the
Desmopressin
4464843
groups other than type O are at a two- to fourfold relative risk. O blood group is associated with reduced levels of von Willebrand factor – because of increased clearance – and factor VIII, which is related to thrombotic risk . A number of acquired conditions augment the risk of thrombosis. A prominent example is antiphospholipid syndrome, which is caused by antibodies against constituents of the cell membrane, particularly lupus anticoagulant (first found in people with the disease systemic lupus erythematosus but often detected in people without the disease), anti-cardiolipin antibodies, and anti-β-glycoprotein 1 antibodies; it is therefore regarded as
Thrombophilia
17454765
Glycoprotein Ib-IX-V Receptor Complex The GPIb-IX-V complex is a profuse membrane receptor complex originating in megakaryocytes and exclusively functional on the surface of platelets. It primarily functions to mediate the first critical step in platelet adhesion, by facilitating binding to von Willebrand factor (VWF) on damaged sub-endothelium under conditions of high fluid shear stress. Although the primary ligand for the GPIb-V-IX receptor is VWF, it can also bind to a number of other ligands in the circulation such as thrombin, P-selectin, factor XI, factor XII, high molecular weight kininogen as well as bacteria. GPIb-IX-V offers a critical role in thrombosis,
Glycoprotein Ib-IX-V Receptor Complex
2091323
characterized by its decreased ability to bind to GPIb receptor on the platelet membrane and normal capability at multimerization. The vWF antigen levels are normal. The ristocetin cofactor activity is decreased and high molecular weight large vWF multimers are present in the circulation. This is a deficiency of the binding of vWF to coagulation factor VIII. The vWF antigen test is normal, indicating normal quantity of vWF. The ristocetin cofactor assay is normal. Assay for coagulation factor VIII revealed marked quantitative decrease equivalent to levels seen in hemophilia A. This has led to some vWD type 2N patients being misdiagnosed
Von Willebrand disease
11327736
processing sites. Some of its substrates are - transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. Alternatively spliced transcript variants encoding different isoforms have been identified. PCSK6 also cleaves and activates corin, a serine protease that regulates sodium homeostasis and blood pressure. This gene is thought to play a role in tumor progression. PCSK6 deficiency causes salt-sensitive hypertension in mice. PCSK6 Proprotein convertase subtilisin/kexin type 6 is an enzyme that in humans is encoded by the "PCSK6" gene. "PCSK6" is a protease that cleaves NODAL into an active form to help trigger the development of left/right (LR)
PCSK6
6335640
of 1876 to 1922, totalling 19 cases on families with bleeding diatheses. The earlier authors attributed the condition to hemophilia (even in the cases of females) or to thrombopathy, which was discovered shortly before as the cause of what had previously been known as purpura hemorrhagica or Werlhof's disease. Von Willebrand also conducted hematological examinations on Hjördis and some of her family members. He recorded a normal or slightly reduced number of platelets and an undisturbed clot retraction, unlike Glanzmann's thrombasthenia. The bleeding time (Duke) was greatly prolonged, extending to more than 2 hours in some cases, while the clotting
Erik Adolf von Willebrand
11664924
the Collagen/Epinepherine membrane. A normal Col/Epi closure time (<180 seconds) excludes the presence of a significant platelet function defect. If the Col/Epi closure time is prolonged (>180 seconds), the Col/ADP test is automatically performed. If the Col/ADP result is normal (<120 seconds), aspirin-induced platelet dysfunction is most likely. Prolongation of both test results (Col/Epi >180 seconds, Col/ADP >120 seconds) may indicate the following; Once anemia and thrombocytopenia have been excluded, further evaluation to exclude von Willebrand disease and inherited/acquired platelet dysfunction can be made. PFA-100 The PFA-100 (Platelet Function Assay or Platelet Function Analyser) is a platelet function analyser that
PFA-100
1537705
is an autosomal recessive hereditary disorder, and can cause discomfort to the dog when it attempts to chew. The progression of the condition usually slows down between eleven and thirteen months of age, and is sometimes followed by a slow partial or complete regression. This condition has also been seen in other breeds of dog, such as the West Highland White Terrier, Cairn Terrier, Boston Terrier, as well as some larger breeds such as Bullmastiffs. Von Willebrand's disease is a hereditary bleeding disorder found in both dogs and humans. It is caused by a lack of von Willebrand factor which
Scottish Terrier
8059061
in motifs such as Arg–X–X–Arg and Lys/Arg–Arg. Cleavage usually results in activation of the proprotein but can also inactivate or modify the activity. Therefore, it is not surprising that it plays a major role in many physiological processes and pathologies, including cancer. Some of its substrates are: proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. A furin-like pro-protein convertase has been implicated in the processing of RGMc (also called hemojuvelin). Both the Ganz and Rotwein groups demonstrated that furin-like proprotein convertases (PPC) are responsible
Proprotein convertase
13368688
as TEM should be used in surgical procedures where major blood loss followed by the need for transfusions can be expected. Like any other haemostasis evaluating method, TEM (and thrombelastography) have limitations which need to be considered when interpreting the results. The typical assays are not responsive for the effect of von Willebrand factor or platelet antagonists such as aspirin or thienopyridines (e.g. clopidogrel), and only supratherapeutic doses of GPIIb/IIIa antagonists may influence results. The sensitivity for coagulation factor deficiencies, including those induced by oral anticoagulation, is less pronounced as compared to clotting assays. Therefore, TEM is not meant to
Thromboelastometry