Hemostasis and Disorders Flashcards
First Step of Hemostasis
Transient constriction of vessel
Mediated by Neural Stimulation and Endothelian from nearby endothelial cells
Major source of vWF?
Stored in what?
Binds to what?
Endothelial Cells in Weibel-Palade Bodies
Subendothelial collagen
Platelet dump which mediators
and for what?
ADP - induces GP2b3a
Thromboxane A-2 (TXA2) - derived of platelet cyclo-oxygenase; further platelet aggregation.
Essential for Platelet aggregation
Essential for Platelet binding to vWF
GP2b3a
GP1b
Sx of Primary Hemostasis Disorders
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.
ITP Idiopathic thrombocytopenic purpura
Cause, Location, Prognosis
Labs
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
Microangiopathic Hemolytic Anemia:
Pathologic Formation of Platelet microthrombi
TTP and HUS
Schistocyte and Hemolysis on platelet plugs.
Used up Platelets- normal megakaryoctes
Normal PT/PTT - not coagulation problem
Thrombotic Thrombocytopenic Purpura
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
Hemolytic Uremic Syndrome due to endothelial damage by drugs or infection
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
TTP predominant problem?
distinguish from HUS
CNS Abnormalities
HUS predominant problem?
distinguish from TTP
Renal insufficiency
Bernard-Soulier Syndrome
“Quality” problem. Not quantity.
Genetic GP1b deficiency- impaired adhesion
mild thrombocytopenia, enlarged platelets
Glanzmann Thrombasthenia
Genetic G2b3a deficiency, platelet aggregation impaired.
How does Aspirin work?
Irreversibly inactivates cyclooxygenase, causing lack of TXA2, which impairs platelet aggregation
Hemophilia A
F-VIII deficiency X-Linked - New Mutations Deep Tissue, Joint, Post-Surgery Bleeding Increase PTT, Normal PT Normal Platelet count and Bleeding Time
Hemophilia B
F-IX Deficiency
Resembles A Clinically
Coagulation Factor Inhibitor
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.
von Willebrand Disease
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.
Vitamin K Deficiency
Gamma Carboxylate 2, 7, 9, 10, C, and S.
Activated by Epoxide Reductase
HIT - Heparin-Induced Thrombocytopenia
IgG response to PF4-HEP complex, releasing fragments, activating other platelets, leading to thrombosis by activating other platelets.
Disseminated Intravascular Coagulopathy (DIC)
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
DIC results as complication of …
Obstetric complication
Sepsis (endotoxin o macrophage IL-1, TNF)
Adenocarcinoma’s Mucin
Acute promyelocytic leukemia’s primary granules
Rattlesnake Bite
Distinguish DIC from Disorder of Fibrinolysis
Increase PT/PTT
Increase Bleeding Time with NORMAL platelet count
Increase Fibrinogen split products without D-dimers
Aminocaproic Acid
Blocks activation of Plasminogen
