(MHD) Abnormal Hemostasis I and II Flashcards
Thrombocytopenia (what is it and what may occur as a result?)
A decreased platelet count. Results in bleeding.
Thrombocytosis (what is it and what may occur as a result?)
An increased platelet count. BOTH bleeding and thrombosis may occur.
What are the main causes for thrombocytopenia? (7)
- Alterations in bone marrow
- Hereditary
- Abnormal hematopoiesis (acquired) ex. B12/Folate deficiency
- Drug-induced (ex. heparin)
- Dilutional (ex. hemodialysis)
- ITP/TTP
- HUS
What is the main drug associated with Drug Induced thrombocytopenia? How does it function?
Heparin
Heparin is an anticoagulant. Heparin causes release of PF-4 from platelets and forms a complex with it, causing its structure to change (it looks foreign). Antibodies bind to it and cause death of platelets.
ITP
Immune thrombocytopenic purpura
Causes an IgG mediated opsonization and phagocytosis of platelets, pulling them from circulation.
TTP
Thrombotic thrombocytopenic purpura
The body activates platelets without any trigger and they clump together endogenously and block small vessels. This is called microangiopathic syndrome.
What are the main causes for thrombocytosis? (3)
- Splenectomy
- Reactive thrombocytosis (ex. due to infection or cancer)
- Autonomous thrombocytosis (clonal disorder)
Storage pool disease
Congential disorder in which there is a decrease in dense granule content. This leads to a lack of aggregation. Rare.
Polycythemia vera
A neoplasm in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets.
Non-thrombocytopenic purpuras
Vascular disorders which cause easy bruising, bleeding from mucosa, purpuras, etc. Platelet function and coagulation are normal. Often difficult to diagnose.
The most common forms of endothelial disorders related to clotting are ___________ (acquired or congenital).
Congenital
What is the main mechanical disorder associated with clotting issues? What is the main nutritional disorder?
Mechanical: increased transluminal pressure
Nutritonal: Scurvy (vitamin C deficiency)
Describe Factor V Lieden and what occurs as a result.
What is it also known as?
Factor V is a cofactor for factor X (which activates Thrombin)
During Factor V Lieden, there is a Factor V point mutation which occurs and makes favtor V non-susceptible to protein C. The net effect is a loss of regulation, amplification goes uncontrolled and you have thrombosis. Also known as activated protein C resistance.
Hemophilia A vs Hemophilia B
What is the big thing they have in common
Hemophilia A: Factor VIII (Classic hemophilia)
Hemophilia B: Factor IX
They are the most common coagulation defects
Which coagulation cascade pathway is the least likely to have a congenital defect?
The extrinsic pathway
How is hemophilia passed genetically? What effect does this disease have on platelet counts?
Both hemophilias are sex-linked recessive. They have no effects on platelet count.
Differentiate between type-1/type-3 von WIllebrand’s disease and type-2 von Willebrand’s disease
Type-1 and Type-3 disease are characterized by a decrease in the circulating level of the factor (i.e. a quantitative defect)
Type-2 is characterized by a qualitative defect in the protein
Hemophilias vs Von Willebrand’s Diseases (APTT changes? Platelet function? Bleeding time?)
Hemophilias:
- APTT prolongation
- Platelet function is normal
- No effect on bleeding time
Von Willebrand’s Disease:
- APTT slightly elevated due to mild reduction in factor VIIIc
- Impaired adhesion of platelets to collagen
- Bleeding time elevated
Primary fibrinolysis
What syndrome is this condition often seen in?
Plasmin breaks down fibrinogen only, forming fibrinogen degradation products. Results in loss of clotting and bleeding as a result.
This condition is seen in dead fetus syndrome (Abruptio Placenta)
What is secondary fibrinolysis?
In secondary fibrinolysis both fibrin and fibrinogen are digested by plasmin. Secondary finbinolysis is also associated with digestion of clotting factors and consumption of platelets.
What is DIC? Describe the pathogenesis.
Disseminated intravascular coagulation
As a result of massive tissue destruction or sepsis (due to bacterial LPS), tissue factor is upregulated. This leads to to widespread microvascular thrombosis and vascular occlusion. This also leads to an activation of plasmin that causes secondary fibrinolysis and bleeding. In other words there is both clotting and bleeding.
What is the hallmark test for DIC?
The D-dimer test is the hallmark for DIC, as D-dimer is a product of fibrinolysis.
A deficiency in a2-antiplasmin leads to…
Increased fibrinolysis and bleeding because Plasmin operates unopposed.
