Hemostasis and Disorders

Question 1

First Step of Hemostasis

Answer 1

Transient constriction of vessel

Mediated by Neural Stimulation and Endothelian from nearby endothelial cells

Question 2

Major source of vWF?
Stored in what?
Binds to what?

Answer 2

Endothelial Cells in Weibel-Palade Bodies

Subendothelial collagen

Question 3

Platelet dump which mediators

and for what?

Answer 3

ADP - induces GP2b3a

Thromboxane A-2 (TXA2) - derived of platelet cyclo-oxygenase; further platelet aggregation.

Question 4

Essential for Platelet aggregation

Essential for Platelet binding to vWF

Answer 4

GP2b3a

GP1b

Question 5

Sx of Primary Hemostasis Disorders

Answer 5

Epistaxis, Hemoptysis, GI Bleeding, Hematuria, and Menorrhagia. Intracranial Bleeding occurs with severe thrombocytopenia. Petechiae or Purpura or Ecchymoses; easy bruising. Petechiae are usually only in qualitative disorders.

Question 6

ITP Idiopathic thrombocytopenic purpura
Cause, Location, Prognosis
Labs

Answer 6

Auto-immune IgG against platelet antigen.
Most common cause in Adult and Child.
Plasma Cells of Spleen. Splenectomy
Consumed by splenic Macrophages. 
Acute:Children:Supportive:Self-resolve
Chronic:Adult:Associated with others
Low Platelet, Normal PT/PTT, megakarocytes
Corticosteroid, chronic relapses

Question 7

Microangiopathic Hemolytic Anemia:
Pathologic Formation of Platelet microthrombi
TTP and HUS

Answer 7

Schistocyte and Hemolysis on platelet plugs.
Used up Platelets- normal megakaryoctes
Normal PT/PTT - not coagulation problem

Question 8

Thrombotic Thrombocytopenic Purpura

Answer 8

Platelet Microthrombi formed 
ADAMS-TS-13 chops up multimers of vWF
Adult Female, Auto-immune
Skin and mucosal bleeding
Microangiopathic hemolytic anemia, Fever
Renal Insufficiency and CNS abnormalities

Question 9

Hemolytic Uremic Syndrome due to endothelial damage by drugs or infection

Answer 9

E.Coli O157H7 verotoxin damages endothelial cells: kidney and brain and ADAMSTS13. Results in Microangiopathic hemolytic anemia and thrombocytopenia. Patient has dysentary, skin and mucosal bleeding, fever, renal and CNS abnormalities

Question 10

TTP predominant problem?

distinguish from HUS

Answer 10

CNS Abnormalities

Question 11

HUS predominant problem?

distinguish from TTP

Answer 11

Renal insufficiency

Question 12

Bernard-Soulier Syndrome

“Quality” problem. Not quantity.

Answer 12

Genetic GP1b deficiency- impaired adhesion

mild thrombocytopenia, enlarged platelets

Question 13

Glanzmann Thrombasthenia

Answer 13

Genetic G2b3a deficiency, platelet aggregation impaired.

Question 14

How does Aspirin work?

Answer 14

Irreversibly inactivates cyclooxygenase, causing lack of TXA2, which impairs platelet aggregation

Question 15

Hemophilia A

Answer 15

F-VIII deficiency
X-Linked - New Mutations
Deep Tissue, Joint, Post-Surgery Bleeding
Increase PTT, Normal PT
Normal Platelet count and Bleeding Time

Question 16

Hemophilia B

Answer 16

F-IX Deficiency

Resembles A Clinically

Question 17

Coagulation Factor Inhibitor

Answer 17

Acquired antibody against a factor, typically F-VIII, so resembles Hemophilia A.
Distinguish with “mixing” study; PTT does not correct with mixing of normal plasma.

Question 18

von Willebrand Disease

Answer 18

Genetic vWF Deficiency
Most common inherited coagulation disorder: Qualitative or Quantitative
Most common is Auto-dominant with decreased vWF levels.
Mild Mucosal and Skin Bleeding
Increase Bleeding Time, Increased PTT (wFV stabilized F-VIII) and normal PT with abnormal Ristocetin Test.
Treat with Desmopressin- increases release of vWF from Weibel-Palade bodies.

Question 19

Vitamin K Deficiency

Answer 19

Gamma Carboxylate 2, 7, 9, 10, C, and S.

Activated by Epoxide Reductase

Question 20

HIT - Heparin-Induced Thrombocytopenia

Answer 20

IgG response to PF4-HEP complex, releasing fragments, activating other platelets, leading to thrombosis by activating other platelets.

Question 21

Disseminated Intravascular Coagulopathy (DIC)

Answer 21

pathologic activation of Coag Cascade
widespread microthrombi -> ischemia and infarction. Consumes platelets and factors, leading to bleeding.
Increases PT/PTT
Microangiopathic Hemolytic Anemia - Schistocytes
Elevated D-dimer

Question 22

DIC results as complication of …

Answer 22

Obstetric complication
Sepsis (endotoxin o macrophage IL-1, TNF)
Adenocarcinoma’s Mucin
Acute promyelocytic leukemia’s primary granules
Rattlesnake Bite

Question 23

Distinguish DIC from Disorder of Fibrinolysis

Answer 23

Increase PT/PTT
Increase Bleeding Time with NORMAL platelet count
Increase Fibrinogen split products without D-dimers

Question 24

Aminocaproic Acid

Answer 24

Blocks activation of Plasminogen