The rest of hemostasis disorders

Question 1

What is hemostasis? What does it help do?

Answer 1

Integrity of bv is necessary to carry blood to tissues;

damage to the wall is repaired by HEMOSTASIS, which involves formation of a THROMBUS (CLOT) at the site of vessel injury

Question 2

Hemostasis occurs in ____ stages; what happens during these stage(s)?

Answer 2

two;

1. primary: forms weak platelet plug and is mediated by interaction between platelets and vessel wall
2. secondary: stabilizes the platelet plug and is mediated by the coag cascade

Question 3

Step 1 of primary hemostasis is

Answer 3

transient vasoconstriction of damaged vessel: mediated by REFLEX NEURAL STIM and endothelin release from endothelial cells

My quick REFLEXES caused me to flex (constrict) and erupt (endothelin) with energy (endothelial cells)

Question 4

Step 2 of primary hemostasis is

Answer 4

platelet adhesion to the surface of disrupted vessel:

1. vWF binds exposed subendothelial collagen
2. platelets bind vWF using the GPIb receptor
3. vWF is derived from the Weibel-Palade bodies of endothelial cells and alpha-granules of platelets

Question 5

Step 3 of primary hemostasis is

Answer 5

Platelet degranulation:

1. adhesion induces shape change in platelets and degranulation with release of multiiple mediators: ADP is released from platelet dense granules; promotes exposure of GPIIb/IIIa receptor on platelets;
   then. ..TXA2 is synthesized by platelet cyclooxygenase (COX) and released; promotes platelet aggregation

A Double Penetration with Good Pussy is seen in TeXAs for those with big COX

Question 6

Step 4 of primary hemostasis is

Answer 6

platelet aggregation:

1. platelets aggregate at site of injury via GPIIb/IIIa using fibrinogen (from plasma) as a linking molecule; results in formation of platelet plub
2. Platelet plug is weak; coagulation cascade (secondary hemostasis) stabilizes it

Question 7

What are disorders of primary hemostasis usually due to? How is it divided? List some clinical features

Answer 7

abnormalities in platelets: divided into quantitative or qualitative disorders
1. Mucosal bleeding: epistaxis (most common symptom), hemoptysis, GI bleeding, hematuria, and menorrhagia; maybe intracranial bleeding with severe thrombocytopenia
2. Skin bleeding: petechiae (1-2 mm), purpura (>3 mm), ecchymoses (>1 cm), easy bruising;
petechaie sign of thrombocytopenia and usually not seen with QUALITATIVE DISORDERS!!

The bitch’s nose started bleeding FIRST. Then she started complaining about coughing up some blood. She had to go to the HS bathroom to shit out and piss out blood. Then her menstrual cycle came up and she was bleeding then too. Found out she died because of some bleeding in her brain. Unlucky girl…

Question 8

Useful lab studies of primary hemostasis include

Answer 8

1. platelet count (normal is 150-400 K/uL; <50 K/uL lead to symptoms
2. Bleeding time: normal 2-7 minutes; prolonged with quantitative and qualitative platelet disorders
3. Blood smear: used to to assess number and size of platelets
4. Bone marrow biopsy: used to assess MEGAKARYOCYTES, which produce platelets

Question 9

Qualitiative platelet disorders include

Answer 9

1. Bernard Soulier syndrome: genetic GPIb deficiency where platelet adhesion is impaired (blood smear shows mild thrombocytopenia with enlarged platelets)
2. Glanzmann thrombasthenia: genetic GPIIb/IIIa deficiency; platelet aggregation impaired
3. Aspirin irreversibly inactivates COX; lack of TXA2 impairs aggregation
4. Uremia disrupts platelet funcion: both adhesion and aggregation are IMPAIRED!!

Bobby Stuver’s Girlfriend Talks A lot:
Bernard Soulier, Glanzmann Thrombasthenia, TXA2, Aspririn

Question 10

What is secondary hemostasis and how do you get the necessary factors?

Answer 10

Stabilizes weak platelet plug via coag cascade
1. Coag cascade generates thrombin, converting fibrinogen to platelet plub fibrin
2. Fibrin cross-linked, yielding a stable platelet-fibrin thrombus;
factors of coag cascade produced by the liver in an inactive state: activation requires:
a. exposure to activating substance (tissue thromboplastin activates factor VII in extrinsic, subendothelial collagen activates factor XII in intrinsic)
b. phospholipid surface of platelets
c. calcium (derived from platelet dense granules)

Question 11

What are disorders of secondary hemostasis due to? Clinical features and labs?

Answer 11

1. Factor abnormalities
2. Deep tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures (like circumcision and wisdom tooth extraction)
3. PT: measures extrinsic (factor VII) and common (factors II, V, X, and fibrinogen) pathways of coag cascade;
   PTT: measures intrinsic (factors XII, XI, IX, and VIII) and common (factors II, V, X, and fibrinogen) pathways of the coag cascade

When I was sitting in Sawgrass hospital, I noticed that blood was going into my MUSCLES and JOINTS. Then, after the WISDOM TEETH EXTRACTION, I noticed there was MORE BLEEDING. I was scared!!

Question 12

Coag factor inhibitor is what? Difference from hemo A?

Answer 12

1. acquired Ab against a coag factor resulting in impaired factor function; anti-FVIII most common;
2. clinical and lab findings similar to hemo A, BUT PTT won’t correct upon mixing normal plasma with patient’s plasma due to inhibitor;
   but PTT would correct in hemo A

Question 13

Vit K deficiency is what? When do deficiencies occur?

Answer 13

1. Multiple coagulation factor function disrupted (vit K activated by epoxide reductase in liver; activated vit K gamma carboxylates factors II, VII, IX, X, and proteins C and S; NEED GAMMA CARBOXYLATION for factor function;
2. Newborns (lack of GI colonization by bacteria that would normally synthesize vit K; vit K injection is prophylactic for all newborns at birth to prevent hemorrhage of newborn
3. Long-term antibiotic therapy: disrupts vit K-producing bacteria in GI tract
4. Malabsorption: deficiency of fat-soluble vitamins

Question 14

Other causes of abnormal secondary hemostasis?

Answer 14

1. Liver failure: decreased production of coag factors and decreased activation of vit K by epoxide reductase (effect of liver failure on coag is followed using PT)
2. Large-volume transfusion: dilutes coag factors, resulting in relative deficiency

Question 15

For hep-induced thrombocytopenia, how does this happen? Consequence?

Answer 15

1. Platelet destruction that arises secondary to heparin therapy
2. Fragments of destroyed platelets may activate remaining platelets, leading to thrombosis

Question 16

How does fibrinolysis normally work? What are disorders due to? Presentation? Labs? Treatment?

Answer 16

1. Normal fibrinolysis removes thrombus after damaged vessel heals: tPA converts plasminogen to plasmin, then plasmin cleaves fibrin and serum fibrinogen, destroying coag factors and blocking platelet aggregation, and alpha2-antiplasmin inactivates plasmin
2. Due to plasmin overactivity resulting in excessive cleavage of serum fibrinogen: radical prostatectomy (urokinase released activates plasmin) and cirrhosis of liver (reduced alpha2-antiplasmin production)
3. Increased bleeding (like DIC)
4. Increased PT/PTT (destroyed coag factors); increased bleeding time WITH normal platelet count, as plasmin BLOCKS PLATELET AGGREGATION; increased fibrinogen split products WITHOUT D-dimers, as serum fibrinogen is lysed but D-dimers can’t form because of no fibrin thrombi
5. aminocaproic acid, blocking activation of plasminogen

Question 17

Basic principles of thrombosis; chracteristics; major risk factors

Answer 17

1. Pathologic formation of an IV blood clot (thrombus): can occur in artery or vein, most commonly in deep veins
2. lines of Zahn (alternating layers of platelets/fibrin and RBCs, and attachment to vessel wall)
3. Three major risk factors: disruption in blood flow, endothelial damage, hypercoag state (Virchow triad)

Question 18

What in blood flow could increase risk for thrombosis? Examples?

Answer 18

1. Stasis and turbulence, since normally blood is continuous and laminar, keeping platelets and factors dispersed and activated
2. Immobilization (DVT risk), cardiac wall dysfunction (arrhythmia or MI) and aneurysm

Question 19

What does endothelial cell damage do? How do they prevent thrombosis risk?

Answer 19

1. disrupts protective function of endothelial cells, increasing thrombosis risk
2. Block exposure to subendothelial collagen and underlying tissue factor, prostacyclin and NO production for vasodilation and platelet aggregation inhibition, heparin-like mc secretion (augment antithrombin III to inactive thrombin and coag factors), tPA secreted, thrombomodulin secreted (redirects thrombin to activate protein C, which inactivates factors V and VIII

In the SEC, players will say NO when you want to touch their PROSTATE. If they go to ATwater to play football, They can PlAy and THRow the ball around

Question 20

For endothelial cell damage, what can cause it? What can lead to the high levels that cause this damage? Presentation of one of these causes?

Answer 20

1. Atheroscelrosis, vasculitis, and high homocysteine levels;
2. Vit B12 and folate deficiency result in mildly elevated homocysteine levels, increasing thrombosis risk (see other flash card for mechanism);
   cystathionine beta synthase (CBS) deficiency results in high homocysteine levels with homocystinuria (CBS converts homocysteine to cystationine): characterized by vessel thrombosis, mental retardation, lens dislocation, and long slender fingers

Without CBS, we’d be stuck with homos with creepy long fingers, retarded, need glasses (lens dislocation), and look pale (vessel thrombosis)

Question 21

What is a hypercoag state due to? Presentation? Mechanism? Specific causes of this state? Treatment?

Answer 21

1. Excess procoagulant proteins or defective anticoagulant proteins (maybe acquired or inherited)
2. Recurrent DVTs or DVTs at young age (mostly deep veins, but also hepatic and cerebral veins)
3. Protein C or S deficiency (autosomal dominant) decreases neg feedback on coag cascade (these proteins inactivate factors V and VIII; they also increase risk for warfarin skin necrosis as initial stage of warfarin therapy leads to temp deficiency of proteins C and S (shorter half-life) relative to factors II, VII, IX, and X, and severe deficiency could be seen at onset of warfarin therapy
4. Factor V Leiden (lacks clevage site for deactivation by proteins C and S: most common inherited cause of hypercoag state); prothrombin 20210A an inherited point mutation in prothrombin resulting in increased gene expression (more thrombin);
   ATIII deficiency decreases protective effect of heparin-like molecules made by endothelium (PTT won’t rise with standard heparin dosing and you need coumadin)
   Oral contraceptives: estrogen induces increased production of coag factors

The Offensive Coordinator ESTimates he will COoperate