(MHD) Abnormal Hemostasis I and II

Question 1

Thrombocytopenia (what is it and what may occur as a result?)

Answer 1

A decreased platelet count. Results in bleeding.

Question 2

Thrombocytosis (what is it and what may occur as a result?)

Answer 2

An increased platelet count. BOTH bleeding and thrombosis may occur.

Question 3

What are the main causes for thrombocytopenia? (7)

Answer 3

1. Alterations in bone marrow
2. Hereditary
3. Abnormal hematopoiesis (acquired) ex. B12/Folate deficiency
4. Drug-induced (ex. heparin)
5. Dilutional (ex. hemodialysis)
6. ITP/TTP
7. HUS

Question 4

What is the main drug associated with Drug Induced thrombocytopenia? How does it function?

Answer 4

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.

Question 5

ITP

Answer 5

Immune thrombocytopenic purpura

Causes an IgG mediated opsonization and phagocytosis of platelets, pulling them from circulation.

Question 6

TTP

Answer 6

Thrombotic thrombocytopenic purpura

The body activates platelets without any trigger and they clump together endogenously and block small vessels. This is called microangiopathic syndrome.

Question 7

What are the main causes for thrombocytosis? (3)

Answer 7

1. Splenectomy
2. Reactive thrombocytosis (ex. due to infection or cancer)
3. Autonomous thrombocytosis (clonal disorder)

Question 8

Storage pool disease

Answer 8

Congential disorder in which there is a decrease in dense granule content. This leads to a lack of aggregation. Rare.

Question 9

Polycythemia vera

Answer 9

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.

Question 10

Non-thrombocytopenic purpuras

Answer 10

Vascular disorders which cause easy bruising, bleeding from mucosa, purpuras, etc. Platelet function and coagulation are normal. Often difficult to diagnose.

Question 11

The most common forms of endothelial disorders related to clotting are ___________ (acquired or congenital).

Answer 11

Congenital

Question 12

What is the main mechanical disorder associated with clotting issues? What is the main nutritional disorder?

Answer 12

Mechanical: increased transluminal pressure

Nutritonal: Scurvy (vitamin C deficiency)

Question 13

Describe Factor V Lieden and what occurs as a result.

What is it also known as?

Answer 13

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.

Question 14

Hemophilia A vs Hemophilia B

What is the big thing they have in common

Answer 14

Hemophilia A: Factor VIII (Classic hemophilia)

Hemophilia B: Factor IX

They are the most common coagulation defects

Question 15

Which coagulation cascade pathway is the least likely to have a congenital defect?

Answer 15

The extrinsic pathway

Question 16

How is hemophilia passed genetically? What effect does this disease have on platelet counts?

Answer 16

Both hemophilias are sex-linked recessive. They have no effects on platelet count.

Question 17

Differentiate between type-1/type-3 von WIllebrand’s disease and type-2 von Willebrand’s disease

Answer 17

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

Question 18

Hemophilias vs Von Willebrand’s Diseases (APTT changes? Platelet function? Bleeding time?)

Answer 18

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

Question 19

Primary fibrinolysis

What syndrome is this condition often seen in?

Answer 19

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)

Question 20

What is secondary fibrinolysis?

Answer 20

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.

Question 21

What is DIC? Describe the pathogenesis.

Answer 21

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.

Question 22

What is the hallmark test for DIC?

Answer 22

The D-dimer test is the hallmark for DIC, as D-dimer is a product of fibrinolysis.

Question 23

A deficiency in a2-antiplasmin leads to…

Answer 23

Increased fibrinolysis and bleeding because Plasmin operates unopposed.