Clotting diseases

Question 1

Glanzmann thrombasthenia

Answer 1

deficiency in Giib-IIa prevents uncleaved fibrinogen mediated bridging of PLTs

bleeding disorder

Question 2

Coumadin

Answer 2

antagonizes reaction bw factors II, XII, IX , X, and X and Ca (vitamin K dependant factors)

prevents them from being held close together in order to act as an anti-coagulant

Question 3

Factor V Leiden mutation

Answer 3

a. Most common mutation (2-15% of Caucasians) in causing hypercoagulative state

i. Factor V becomes resistant to cleavage by protein C
c. Heterozygous at 5% increased risk, homozygotes at 50% increased risk
i. Risk increases as acquired risk factors are added on (pregnancy, bedrest)
ii. Must consider inherited causes in patients under 50 with thrombosis (EVEN IF other risk factors are present)

Question 4

Prothrombin mutation

G20210A

Answer 4

a. Fairly common (1-2% Caucasians) point mutation
b. Increases serum prothrombin
i. Increases DVT risk by 3x

Question 5

Cystathione B-synthetase deficiency (rare)
or

methyleneterahydrofolate mutation

Answer 5

a. Increases serum homocysteine

ii. Increases risk for arterial and venous thrombosis, and atherosclerosis

Question 6

High risk for thrombosis

Answer 6

Bedrest
MI
Afib
Tissue injury 
Cancer
Prosthetic cardiac valves
DIC
Heparin induced thrombocytoepenia 
antiphospholipid syndrome

Question 7

2. Heparin-induced thrombocytopenia (HIT)

Answer 7

a. Follows admin of unfractionated heparin
i. Antibodies bind platelet bound heparin and platelet factor 4
ii. Results in activation, aggregation, consumption of platelets (i.e. causes thrombocytopenia)
b. Induces a thrombotic state (even though heparin is present)

Question 8

3. Antiphospholipid antibody syndrome

Answer 8

a. Presents with recurrent thrombosis, miscarriages, cardiac valve vegetations, thrombocytopenia

Abs cause endothelial injury

2. May have false positive for syphilis

can be primary or secondary =SLE

primary is catastrophic

Question 9

Trosseau syndrome

Answer 9

disseminated cancer that releases pro-coagulants (mucins)

Question 10

Disseminated intravascular coagulation

Answer 10

i. Potential complication of any condition associated with widespread thrombin activation
ii. Sudden onset of widespread fibrin thrombi in the microcirculation
1. Cause diffuse circulatory insufficiency
2. Consumes platelets and coagulation proteins and activates fibrinolytic cascade
a. causes severe bleeding disorder

Question 11

Septic shock overview

Answer 11

due to vasodilation and peripheral pooling of blood due to systemic immune reaction to microbial (bacteria or fungal) infection

Question 12

septic shock sequelae

Answer 12

often present with vasodilation and have warm/flushed skin and low BP
* thrombosis, DIC, edema, vasodilation

insulin resistance
adrenal insufficiency
immune suppression
organ dysfunction

Question 13

septic shock phases

Answer 13

i. Non-progressive: reflex compensatory mechanisms are activated and perfusion is maintained
(Baroreceptors, catecholamines, RAAS, ADH)
ii. Progressive: hypoperfusion, metabolic imbalance, acidosis

iii. Irreversible cellular and tissue injury, cannot be corrected
(Lysosomal leakage, worsened myocardial function, bacteremia, complete renal shutdown and acute tubular necrosis )

Question 14

Prothrombin time

Answer 14

assess the extrinsic pathway
II, V, VII, X and fibrinogen

add TF to chelated plasma, then add Ca2++

Question 15

fat embolism syndrome

Answer 15

minority of patients who become symptomatic
Fat, RBC, PLT aggregates occlude pulmonary vasculature—>pulmonary insufficiency

anemia and thrombocytopenia

**diffuse petechial rash