Hemostasis Disorders

Question 1

Steps of Primary Hemostasis

Answer 1

1. transient vasoconstriction of damages vessel- endothelin
2. platelet adhesion to the surface of disrupted vessel- vWF binds exposed subendothelial collagen, platelets bind vWF using GP1b
3. platelet degranulation- ADP (exposure of GPIIb/IIIa), TXA2 (promotes platelet agg)
4. platelet aggregation- via GPIIb/IIIa and fibrinogen linkers

Question 2

Immune Thrombocytopenic Purpura (ITP)

Answer 2

autoimmune production of IgG against platelet antigens
most common thrombocytopenia in kids and adults
Ab-bound platelets consumed by splenic MØ
thrombocytopenia, ↓platelets, inc. megakaryocytes, normal PT/PTT
Tx- corticosteroids, IVIG, splenectomy

Question 3

Microangiopathic Hemolytic Anemia

Answer 3

pathologic microthrombi in small vessels, RBCs sheared as they cross microthrombi- cause schistocytes
seen in TTP and HUS

Question 4

Thrombotic Thrombocytopenic Purpura

Answer 4

decreased ADAMTS13 (normally cleaves vWF), causes abnormal platelet adhesion and microthrombi
could include CNS abnormalities
thrombocytopenia w/ inc bleeding time
normal PT/PTT
inc megakaryocytes

Question 5

Hemolytic Uremic Syndrome

Answer 5

endothelial damage by drugs or infection
classic in children with E coli O157:H7 or shigella dysentery (exposure to undercooked beef)
verotoxin- damages endothelial cells and results in platelet microthrombi
could involve renal insufficiency
thrombocytopenia w/ inc bleeding time
normal PT/PTT
inc megakaryocytes

Question 6

Bernard- Soulier syndrome

Answer 6

genetic GPIb deficiency- impaired platelet adhesion

Question 7

Glanzmann thrombasthenia

Answer 7

genetic GPIIb/IIIa deficienty- platelet agg impaired

Question 8

Secondary hemostasis

Answer 8

stabilizes weak platelet plug
thrombin- converts fibrinogen to fibrin, fibrin xlinked, makes stable platelet plug
Activating substances
1.tissue thromboplastin- activates factor VII
subendothelial collagen- activates factor XII
2.phospholipid surface of platelets
3. calcium

Question 9

Hemophilia A

Answer 9

factor VIII deficiency, X-linked recessive, can arise de novo
deep tissue, joint, post-surgical bleeding
inc PTT, normal PT, normal platelets and bleeding

Question 10

Hemophilia B (Christmas disease)

Answer 10

factor IX deficiency
deep tissue, joint, post-surgical bleeding
inc PTT, normal PT, normal platelets and bleeding

Question 11

Coagulation factor inhibitor

Answer 11

acquired AB to a coagulation factor, anti-FVIII most common

PTT does not correct upon mixing pt plasma with normal plasma

Question 12

Von Willebrand Disease

Answer 12

genetic vWF deficiency, most common inherited
AD, decreased vWF levels, inc bleeding time, inc PTT due to decreased FVIII half-life (vWF stabilizes FVIII)
abnormal ristocetin test
tx- desmopression (ADH analogue), increased VWF release from weibel-palade bodies

Question 13

Vitamin K deficiency

Answer 13

activated by epoxide reductase in liver, gamma carboxylates factors 1972, Prot C, S
found in newborns- lack of GI colonization
long-term antibiotic use- disrupts vit K producing bacteria in guy
malabsorption- deficiency of fat-soluble vitamins

Question 14

Heparin- induced thrombocyopenia

Answer 14

platelet destruction 2dary to heparin, platelet factor 4-heparin complex destroyed by spleen, fragments of destroyed platelets may activate remaining- thrombi

Question 15

Disseminated intravascular coagulation

Answer 15

pathologic activation of coagulation cascade
widespread microthrombi- consumption of platelets and coag factors- bleeding esp from IV sites and mucosal surfaces
dec platelets, inc PT/PTT, dec fibrinogen, microangiopathic hemolytic anemia, elevated fibrinogen split products (D-dimer- splitting of xlinked fibrin)

Question 16

DIC causes

Answer 16

most secondary to
obstetric- tissue thromboplastin in amniotic fluid activates coagulation (Factor V)
sepsis- endotoxins from bacterial wall and cytokines induce endothelial cells to make tissue factor
adenocarcinoma- mucin act coag
Acute promyelocytic leukemia- primary granules act coag
Rattlesnake bite- venom act coag

Question 17

Fibrinolysis

Answer 17

removes thrombus, tPA converts plasminogen to plasmin, plasmin cleaves fibrin and serum fibrinogen, destroys coagulation factors, and blocks platelet aggregation
alpha2-antiplasmin- blocks plasmin
aminocaproic acid- blocks plasminogen

Question 18

Protein C/S deficiency

Answer 18

normally inactivate factors V, VIII

increased risk for warfarin skin necrosis

Question 19

Factor V Leiden

Answer 19

mutated form of factor V, lacks cleavage site for Protein C/S, most common inherited hypercoagulable state

Question 20

Prothrombin 20210A

Answer 20

inherited point mutation in prothrombin, increased gene expression, increased thrombin- promotes thrombus

Question 21

ATIII deficiency

Answer 21

ATIII- normally inactivates thrombin and coagulation factors
deficiency- increased risk of rhombus
PTT does not rise with standard heparin dosing (words by activating) ATIII

Question 22

Oral contraceptives

Answer 22

estrogen increases production of coagulation factors, increased risk for thrombosis