Abnormal Hemostasis I and II

Question 1

Quantitative Disorders of platelets

Answer 1

A number of diseases result in a decrease or increase in the number of platelets.

thrombocytopenia, thrombocytosis, thrombocythemia

Question 2

thrombocytopenia

Answer 2

A decreased platelet count results in bleeding

Question 3

thrombocytosis

Answer 3

a benign increase in platelet count

Question 4

thrombocythemia

Answer 4

when it is a clonal proliferation (neoplastic)

Question 5

what causes Thrombocytopenia
s

Answer 5

Alterations in bone marrow

Hereditary thrombocytopenia

Abnormal hematopoiesis (acquired, B12/Folate deficiency, pre-leukemia)

Drug Induced thrombocytopenia (Heparin, gold, quinine, quinidine, sulfonamides, GP IIb/IIIa Inhibitors)

Dilutional (hemodialysis, heart lung machine)

Question 6

what is a possible outcome of heparin complexing with PF-4

Answer 6

Ab are formed to the complex - the Ab lead to activation and aggregation of platelets - can block blood vessels leading to gangrene, ampuation, stroke exc. (complication of Heparin therapy)

Question 7

ITP

Answer 7

Immune thrombocytopenic purpura (IgG mediated)

Question 8

TTP

Answer 8

Thrombotic thrombocytopenic purpura (abnormal vWF multimers), arterial thrombi (platelet-rich)

get many small bruises due to increased bleeding

Question 9

HUS

Answer 9

Hemolytic Uremic Syndrome- thrombocytopenia

Question 10

Splenectomy

Answer 10

thrombocytosis (increased platelet count), platelet function is normal

Question 11

Reactive thrombocytosis

Answer 11

thrombocytosis (increase) due to cancer, infection, drugs.

Question 12

Autonomous thrombocytosis (thrombocythemia)

Answer 12

Platelets ↑ (> 1,000,000/µl): clusters of platelets in circulation. Bleeding may occur.

Question 13

Qualitative Disorders
 of platelets

Answer 13

Platelet numbers are usually normal, however, platelet function is impaired

Question 14

3 causes of qualitative platelet disorders

Answer 14

Disease induced platelet defects (Liver disorders, paraproteinemia)

Drug induced platelet defects (Aspirin, NSAIDS (non-steroidal anti-inflammatory drugs))

Diet induced platelet defects (Omega 3 fatty acids (ocean fish), Eskimos)

Question 15

Inherited Disorders of Platelets


Answer 15

Glanzmann’s thrombasthenia

Bernard-Soulier disease

Storage pool disease (decrease dense granule content, no aggregation )

Other disorders (Purpura of unknown origin - gray platelet syndrome, lack of alpha granules)

Question 16

Glanzmann’s thrombasthenia

Answer 16

Autosomal recessive, GPIIb/IIIa defect, aggregation defect, bleeding time ↑

Question 17

Bernard-Soulier disease

Answer 17

Autosomal recessive, GP Ib defect, adhesion defect, bleeding time ↑

Question 18

polycythemia vera

Answer 18

is 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 19

non-thrombocytopenic purpuras

Answer 19

vascular disorders

common, but do not result in severe bleeding diathesis.

Platelet function and coagulation are normal.

Easy bruising, bleeding from mucosa, purpura, vasculitis.

Question 20

Subendothelial Disorders

Answer 20

Congenital- *Ehler Danlos Syndrome-Hypermobile joints. Hyperflexible skin, osteogenesis imperfecta, drugs, infections, amyloidosis

Acquired- Purpura simplex, amyloids, drugs, steroid purpura (prednisone), Cushing’s syndrome (steroid excess), Henoch-Schonlin purpura (usually drug induced).

Question 21

Endothelial Disorders

Answer 21

Congenital- Most common, hereditary hemorrhagic, telangiectasia (HHT), arteriovenous malformation; giant hemangioma (Kasaback-Merritt syndrome)

Acquired- Inflammation, vasculitis (drugs,viruses, Rickettsia)

Question 22

other types of diseases that cause bleeding disorders

Answer 22

non-thrombocytopenic purpuras
subendothelial disorders
endothelial disorders
mechanical disorders
nutritional disorders

Question 23

Protein C is activated by

Answer 23

thrombin-thrombomodulin with protein S as a cofactor

Question 24

activated Protein C’s function

Answer 24

it is a serine kinase that regulated the coagulation cascade by digesting factors V and VIII

Question 25

protein C resistance

Answer 25

defect in Factor V that prevents it from being degraded by protein C (once activated it is continuously active) can be determined by PCR

Question 26

Hemophilia A defect

Answer 26

factor VIII defect, Classical

Question 27

Hemophilia B defect

Answer 27

factor IX defect, Christmas Disease

Question 28

vitamin K dependent factors

Answer 28

C, S, II, VII, IX, X

Question 29

prothrombin time

Answer 29

a labatory test for extrinsic pathway.

II, V, VII, X and fibrinogen

use blood plasma and add activators to it tos ee how long it takes to clot

Question 30

APTT

Answer 30

lab test for intrinsic pathway activation. VIII, IX, XI and XII (actually measures all factors but FVII, FXIII, protein C and S).

Question 31

hemophilia’s transmission

Answer 31

Both are transmitted as sex linked recessive

Question 32

blood tests in hemophilias

Answer 32

APTT is elevated, no effect on platelets

Question 33

Von Willebrand’s Disease

Answer 33

Hemostatic defect due to von Willebrand factor (ristocetin co-factor, factor VIII antigen) defect.
vW factor binds to platelet receptors (glycoprotein Ib, IIb-IIIa) and to collagen and subendothelium.

Question 34

types of von Willebrand’s disease

Answer 34

1. Type-1 and Type-3 von Willebrand’s diseases are characterized by a decrease in the circulating level of the factor.
2. Type-2 von Willebrand’s disease is characterized by a qualitative defect in the protein.

Question 35

differences in hemophilias vs. von Willebrand’s disease

Answer 35

Hemophilias
APTT prolongation
Platelet function-normal
Bleeding time - no effect

Von Willebrand’s Disease
APTT slightly elevated due to mild reduction in factor VIIIc
Hemostatic function impaired due to impaired adhesion of platelets to collagen in-vivo.
Bleeding time elevated.

Question 36

what occurs in Primary Fibrinolysis

Answer 36

In primary fibrinolysis, only fibrinogen is converted into fibrinogen degradation products.
This condition is seen in dead fetus syndrome (Abruptio Placenta).

Fibrinogen →→→ Fibrinogen degradation products

Question 37

outcomes from primary fibrinolysis

Answer 37

Excessive fibrinolysis can result in bleeding due to decreased fibrinogen levels.

Fibrinogen degradation products can also produce anticoagulant effects.

Overdosage of thrombolytic (t-PA) agents can result in a primary fibrinolytic state and cause bleeding.

Question 38

Secondary Fibrinolysis 
aka

Answer 38

Disseminated intravascular coagulation

Question 39

what occurs during secondary fibrinolysis

Answer 39

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.

commonly occurs when both fibrinolysis and coagulation are activated

get both synthesis and degradation of fibrin simultaneously

Question 40

D-dimer test

Answer 40

can indicate either a DVT or DIC (higher levels with DIC)

Question 41

Deficiency of a2-Antiplasmin

Answer 41

Results in increased fibrinolysis (Bleeding) due to a lack of inhibition on Plasmin

Question 42

a2-Antiplasmin (a2-AP)

Answer 42

inhibits plasmin when it binds to it

Question 43

Drug Induced Bleeding Disorders

Answer 43

Bleeding with thrombolytic drugs.
Bleeding with anticoagulants (Heparin)
Bleeding with drugs
      - Anti-platelet drugs
	  - Thrombolytic drugs
Drug induced thrombocytopenia
Heparin induced thrombocytopenia (HIT)

Question 44

which test is used to diagnose hemophilias

Answer 44

Activated partial thromboplastin time

Question 45

which test is used to monitor therapeutic heparinization in treatment of a DVT

Answer 45

Activated partial thromboplastin time

Question 46

which test is used to monitor anticoagulating status (ie warfarin use)

Answer 46

PT/INR