Overview of Hemostasis and Thrombosis Flashcards
Vascular injury leads to what to events that will both lead to the formation of a hemostatic plug?
Platelet activation and Coagulation activation
What are the 3 steps of platelet function?
adhesion -> Activation -> Aggregation
What are the 3 steps in coagulation?
Activation -> Thrombin Formation -> Fibrin formation, polymerization and Stabilization
What is Primary Hemostasis?
Platelet plug formation
What is secondary Hemostasis?
Fibrin Clot formation (coagulation cascade) Thrombin -> fibrin, with cross linking of fibrin by factor XIIIa
What is the Membrane receptor for Primary hemostasis?
Glycoprotein Ib
What is the adhesive protein for Primary hemostasis?
Von willebrand factor
What is the appropriate surface for primary hemostasis?
Subendothelial matrix
What are the regulators of Secondary Hemostasis?
- serine protease inhibitors (antithrombin)
- Protein C pathway (controls Va and VIIIa)
- Fibrinolytic system (removes excess clot)
What are regulators of Primary Hemostasis?
- NO
- Prostacyclin (PGI2)
- ADPase
How do Antithrombins ?
they basically bind to serine proteases and thrombin and inhibit their action. (SERPIN and HEPARIN both do this)
How does the Protein C system work as a regulator of Secondary hemostasis?
Activated Protein C plus protein S serve to inactivate factors Va and VIIIa.
What happen is there is a deficiency in Protein S or C?
Results in hypercoaguable states
______ is resistance to inactivation by Protein S and C.
Factor V leiden mutation
How does plasmin regulate secondary hemostasis?
Removes excess fibrin clot
What are the screening tests of Hemostasis?
- Prothrombin time
- International Normalized Ratio
- Partial Thromboplastin time
- Platelet count
- Bleeding time
How does the Prothrombin time test work?
- it screens for activtity of proteins in the EXTRINSIC pathway (Factors V, VII, II, X and fibrinogen)
- Phospholipid and TF are added to patients plasma with Ca++
- Time to form clot is noted (11-13 secs)
How does the Partial Thromboplastin time test work?
Screens for activity within the INTRINSIC pathway (Factors XII, XI, IX, VIII, X, V, II and fibrinogen)
- Addition of negatively charged activator of factor XII to patient serum with Ca++
- Clot is formed after 28-35 seconds
What are the Classifications of bleeding disorders?
- Congenital vs. Acquired
- Mild vs. Severe
- Primary vs Secondary
- Regulatory disorder
What are the clinical and lab findings of bleeding disorders of Primary Hemostasis?
Clinical:
- Mucocutaneous bleeding
- Excessive bleeding with trauma
Lab:
- Prolonged BT/PFA-100
- Thrombocytopenia
What are the clinical and lab findings of bleeding disorders of Secondary hemostasis?
Clinical:
- Soft tissue bleeding
- Excessive bleeding with trauma
Lab:
- Prolonged PT and PTT
- Prolonged TT (Thrombin time)
What are the clinical and lab findings of Regulatory bleeding disorders of hemostasis?
Clinical:
- Soft tissue bleeding
- Excessive bleeding with trauma
Lab:
- Normal PT and PTT
- Normal Bleeding time
- Normal platelet count
What are the 3 congenital Bleeding Disorders?
- Von Willebrand disease
- Factor VIII Deficiency
- Factor IX deficiency
Tell me about Von willebrand Disease…
Autosomal dominant disorder due to abnormalitles of vW factor.
- Abnormalities may be quantitative or qualitative
- Mucocutaneous bleeding (nose bleeds) is the dominant clinical manifestation
What are the 3 classes of vWD?
Type 1 = Quantitative (Partial)
Type 2 = Qualitative
Type 3 = Quantitative (total)
What are the clinical manifestations of vWD?
- epistaxis
- Ecchymoses
- mucosal bleeding
- Bleeding with trauma or surgery
- Symptoms often improve post -adolescence
What are the Lab features of vWD?
BT/PFA-100 = prolonged PTT = usually prolonged VIII = decrease to normal vWF :ag: = Decreased to normal vWF :Rcof: = Decreased to normal
What is the Tx for vWD?
- Desmopressin
- Antifibrinolytic agents
- Factor VIII concentrates
- Cryoprecipitate
Tell me about Hemophilia A…..
The most serious bleeding disorder…
- X linked recessive disorder caused by deficiency of factor VII.
- symptoms start in early childhood.
What are the clinical manifestations of Hemophilia A?
- Hemarthosis
- soft tissue bleeding
- Excessive bleeding with trauma
- intramuscular hematomas
- intracerebral hemorrhage
- bleeding into other tissues.
What are the Lab features of Hemophilia A?
BT/PFA-100 = Normal PTT = prolonged VIII = decrease vWF :ag: = normal vWF :Rcof: = normal Factor IX = normal
What are the 3 classes of Hemophilia A?
Severe = 5% Factor VIII
What is the Tx for Hemophilia A?
- Factor VIII concentrates
- Inhibitors of Fibrinolysis
Tell me about Hemophilia B…..
Sex linked recessive disorder caused by deficiency in factor IX.
* Clinical and lab manifestations are similar to deficiency of factor VIII. Can also be mild moderate or severe.
What are the 3 classes of platelet disorders?
Quantitive
Qualitative
Combined
What is the mechanism of Thrombocytopenia?
- Decreased platelet production (Quantitative)
- Increased destruction of platelets
- sequestration
- Congenital vs aquired
How is Thrombocytopenia evaluated?
- Peripheral blood smear
- bone marrow examination
- platelet antibody determination
- Clinical history
Tell me about Acute/Childhood Immune Thrombocytopenic purport (ITP)….
- Viral prodrome common
- sudden onset
- severe thrombocytopenia
- Frequently undergoes remission
- M:F = 1:1
Tell me about Chronic/adult Immune Thrombocytopenic purport (ITP)….
- No antecedent infection
- Gradual onset
- Moderate Thrombocytopenia
- Infrequent remission
- More common in females.
What is the Pathophysiology of ITP?
Autoantibodies directed at the platelet membrane antigens (GPIb/IX and IIb/IIIa are common targets)
*increased IgG bound to the platelet surface promotes increased sequestration/destruction by the reticuloendothelial system.
What are the clinical manifestations of ITP?
- Petechial hemorrhages
- Ecchymoses (brusing)
- Bleeding with trauma or surgery
What bone marrow and blood findings would you expect with ITP?
- Megakaryocyte normal to increased
- No Microangiopathic changes on blood smear review.
What is the treatment for ITP?
- Corticosteroids
- Intravenous immunoglobulin
- Immunosuppression
- Splenectomy
What is Thrombotic Thrombocytopenia Purpura TTP?
An acute disorder characterized by intravascular platelet activation with formation of platelet rich micro thrombi throughout circulation. *can be inherited or acquired
What causes TTP?
a deficiency of ADAMS 13, a metalloprotienase that usually degrades very high molecular weight vWF.
What is DIC?
Unregulated widespread intravascular activation of the hemostatic system.
When does DIC occur?
- Infections
- Tissue Injury (trauma, burn, surgery)
- Obstetrical complications
- Certain malignancies
What are the clinical manifestations of DIC?
- bleeding from multiple sites Thromboembolic problems - Hypotension and shock - respiratory dysfunction - Hepatic dysfunction - Renal dysfunction - CNS dysfunction
What is the Tx for DIC?
- remove/reverse the intuiting stimulus
Supportive therapy with transfusions of blood products: - FFP: coagulation and regulatory proteins
- Cryoprecipitates: fibrinogen, VIII, vWF
- Platelets
