Week 4 Flashcards
Summarize role of vWF in clot formation
· Factor VIII is bound to VWF while inactive in circulation
· VWF binds to collagen when it is exposed inendothelial cellsdue to damage occurring to the blood vessel. Endothelium also releases VWF which forms additional links between the platelets’ glycoprotein Ib/IX/V and the collagen fibrils
· VWF binds to plateletgpIbwhen it forms a complex withgpIXandgpV;
-VWF binds to other platelet receptors when they are activated
Describe the role of factor VIII in hemostasis
· In the blood, it mainly circulates in 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.
pathophysiology of vWD, type I
· The anomalies responsible for type 1 VWD generally lead to intracellular retention or rapid clearance of VWF from the circulation.
· Type 1 von Willebrand disease characterized by partial quantitative plasmatic deficiency of an otherwise structurally and functionally normal Willebrand factor.
causes and inheritance patterns of Type 1 vWD
D cases) is a quantitative defect which is heterozygous for the defective gene. It can arise from failure to secrete vWF into the circulation or from vWF being cleared more quickly than normal.
causes and inheritance patterns of Type 2 vWD
is a qualitative defect and the bleeding tendency can vary between individuals. Four subtypes exist: 2A, 2B, 2M, and 2N. These subtypes depend on the presence and behavior of the underlying multimers.
causes and inheritance patterns of Type 2A vWD
quantitatively normal but qualitatively 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.
causes and inheritance patterns of Type 2B vWD
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 occur. Large vWF multimers are reduced or absent from the circulation.
causes and inheritance patterns of Type 2M vWD
Type 2M vWD is a qualitative defect of vWF 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.
causes and inheritance patterns of Type 2N vWD
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 as having hemophilia A.
causes and inheritance patterns of Type 3 vWD
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.
clinical features of vWD, type I
· Asymptomatic or mild symptoms · Mucosal bleeding · Bleeding following surgery (including dental procedures) · Noticeable easy bruising · Menorrhagia
PT (prothrombin time)
Used to evaluate extrinsic pathway of coagulation. Used to determine clotting tendency of blood, measure of warfarin dosage, liver damage, and Vitamin K status. PT measures Factors I, II, V, VII, and X. The prothrombin time is the time it takes plasma to clot after addition of tissue factor.
PTT
Partial thromboplastin time (PTT) measures the overall speed at which blood clots by means of two consecutive series of biochemical reactions known as the “intrinsic” (now referred to as the contact activation pathway) and common coagulation pathways.The partial thromboplastin time (PTT) is used in conjunction with another measure of how quickly blood clotting takes place called the prothrombin time (PT). The prothrombin time measures the speed of clotting by means of the extrinsic pathway (also known as the tissue factor pathway).
Bleeding time
- Bleeding time is a laboratory test to assess platelet function and the body’s ability to form a clot. The test involves making a puncture wound in a superficial area of the skin and monitoring the time needed for bleeding to stop (ie, bleeding site turns “glassy”).
- A bleeding time evaluation is used to measure the primary phase of hemostasis, which involves platelet adherence to injured capillaries and then platelet activation and aggregation. The bleeding time can be abnormal when the platelet count is low or the platelets are dysfunctional.
how vWF leads to anemia
Hemorrhage can lead to loss of RBC –> anemia
