Hemostasis and Related Disorders Flashcards
End product of primary hemostasis
Platelet plug
End product of secondary hemostasis
Stabilize the weak platelet plug
Immediate response to endothelial damage
Transient vasoconstriction
Function of von Willebrand Factor
Binds to exposed collagen in damaged endothelium and the platelets then bind to the vWF
Platelets bind to vWF via what receptor
Gp1b
Source of von Willebrand factor
Endothelial cell (majority) platelet
Contents and location of Weibel palade body?
vWF and P selectin
found on endothelial cell
Binding of platelets to vWF causes degranulation which releases what substances and function
ADP - causes expression of GpIIbIIIa necessary for aggregation Thromboxane A2 (from platelet COX) - promotes platelet aggregation
Molecule which links platelets together
Fibrinogen
Thrombocytopenia usually presents with?
Mucosal bleeding (hemoptysis, skin, GI, hematuria) (intracranial if severe)
Autoimmune production of IgG against platelet antigens (like GpIIbIIIa)
Immune Thrombocytopenic Purpura
Most common cause of thrombocytopenia in children and adults
Immune Thrombocytopenic Purpura
Where are autoantibodies against platelets produced in ITP
Spleen
Spleen then destroyes these antibody tagged platelets
Lab findings in ITP
low platelet count
normal pt/ptt
increased megakaryocytes (compensation)
Initial Treatment for ITP
Corticosteroids, IVIG
How does IVIg work
Introduce immunoglobulin to body, spleen destroys that immunoglobulin instead of the autoimmune process
Pathologic formation of platelet microthrombi in small vessels
Microangiopathic Hemolytic Anemia
Pathophysiology of hemolytic anemia in Microangiopathic Hemolytic Anemia
If there is microthrombus, RBC passing through narrow vessel is damaged by the thrombus, yielding schistocytes.
What is a schistocyte
Damaged RBC, characteristic of hemolytic anemia
Two types of Microangiopathic Hemolytic Anemia and difference bet two
Thrombotic Thrombocytopenic Purpura - Hemolytic Uremic Syndrome
Enzyme decreased in TTP and function
ADAMSTS13 - degrades (prepares) vWF polymers to monomers for proper platelet adhesion,
if polymers remain, platelet excessively aggregates –> thrombus
Pathophysiology of Hemolytic Uremic Syndrome
Drugs or infection damage endothelium –> microthrombi –> shearing of RBC
Infection associated with HUS
E coli O 157:H7 - releases verotoxin
Clinical findings of TTP and HUS
Both - fever, hemolytic anemia, thrombocytopenia
TTP - CNS abnormality
HUS - Renal insufficiency
Treatment of TTP or HUS
Plasmapheresis, corticosteriois
Genetic Gp1b deficiency, leading to impaired platelet adhesion
Bernard Soulier Syndrome
Blood smear finding in Bernard Soulier syndrome?
Mild thrombocytopenia, enlarged platelets (immature, short lived platelets)
Genetic GpIIbIIIa deficiency
Glanzmann thrombastenia
End product of secondary hemostasis
Generation of thrombin which turns fibrinogen to fibrin, and fibrin is cross linked forming stable platelet plug
Clinical features of disorders of clotting factors
Deep tissue bleeding (muscles and joints), rebleeding after surgery
PT vs PTT
PT - extrinsic and common pathway
PTT - intrinsic and common pathway
Intrinsic, Extrinsic, and common pathwayas (factors only)
Intrinsic - 12 - 11 - 9 - 8 - 10
Extrinsic - 7 - 10
Common - 5 - 2 - 1
What activates the intrinsic pathway?
Subendothelial collagen
What activates the extrinsic pathway?
Tissue thromboplastin
Heparin improves which clotting time?
PTT
Coumadin improves which clotting time?
PT
Disease with factor 8 deficiency, x linked recessive but can arise de novo from mutation
Hemophilia A
Disease with factor 9 deficiency
Hemophilia B, Christmas Disease
Acquired antibody against clotting factors? What is most common?
Clotting factor inhibitor
Anti - Factor 8
Utility of mixing study and logic behind it
Mix normal plasma with patient plasma
If hemophilia - PTT improves (clotting factors of normal plams)
IF clotting factor inhibitor - PTT still deranged (antibody attacks new cloting factors)
Most common inherited coagulation disorder
Von Willebrand disease (vWF deficiency)
Ristocetin test is used for what disease
Von Willebrand disease
Von Willebrand factor helps in stabilizing what clotting factor
Factor 8
Treatment for von willebrand disease
Desmopressin (*increase vWF release from weibel palade bodies)
Vitamin K does which step in the Vit K dependent factors
Gamma carboxylation
What enzyme activates Vitamin K and in what organ
Epoxide reductase - liver
Pathology of heparin induced thrombocytopenia
Heparin binds to platelet factor 4, which leads to IgG mediated platelet destruction, , then fragments activate other platelets leading to thrombosis
Pathologic activation of coagulation cascade
Disseminated Intravascular coagulation
Clinical features of DIC
Ischemia and infarction from coagultion
Mucosal bleeding from consumption of platelets and factors
What reptile when bites can cause DIC
Rattlesnake
Product from splitting of cross linked fibrin during fibrinolysis
D-dimer
This is why used for screening DIC, pulmo embo
What converts plasminogen to plasmin
tissue Plasminogen Activator
Functions of plasmin
- breaks fibrin
- breaks fibrinogen
- breaks clotting factors
- prevents platelet aggregation
What molecule inactivates plasmin?
Where is it produced?
Alpha 2 anti-plasmin
Liver
This blocks activation of plasminogen, which can be used for treating disorders of fibrinolysis
Aminocaproic acid
Features of a thrombus which differentiates it from postmortem clot
- Lines of Zahn
2. Attached to vessel wall
What are Lines of Zahn
Layer of alternating blood cells and fibrin found in thrombosis
What is Virchow’s Triad
Hypercoagulable state
Stasis/Turbulence
Endothelial Cell Damage
Deficiency of which vitamins can lead to homocystenuria?
Folate and B12
Characterized by vessel thrombosis,mental retardation long slender fingers, and lens dislocation from elevated homocysteine levels
Cystathionine beta synthase deficiency
Protein C and Protein S function?
Inactivate Factor 5 and 8
Pathophysiology of Warfarin skin necrosis
Protein c AND s are destroyed before vitamin K is, so less anticoagulant means more thrombosis in the skin, hence name
What is Factor V Leiden
Mutated form of Factor V with no cleavage site for protein C and S
Most common inherited cause of hypercoagulable state
Factor V Leiden
Inherited point mutation in prothrombin
Prothrombin 20210A
Decreased protective effect of heparin like molecules on endothelium
Antithrombin III deficiency
antithrombin prevents excessive clotting
Effect of estrogen on coagulation factors
Increased coagulation factor production –> increased thrombosis
Feature of atherosclerotic embolus
Cholesterol clefts in embolus
Bends and Chokes are associated with?
Decompression sickness (Nitrogen embolism) Muscle and joint pain; respiratory distress
Chronic form of decompression sickness associated with multifocal ischemic necrosis of bone
Caisson disease
Sustance in amniotic fluid which triggers coagulation cascade and may lead to DIC
Tissue Thromboplastin
Histologic findings in amniotic fluid embolus
Squamous cells and keratin debris
Gross appearance of pulmonary infarction
Hemorrhagic wedge shaped infarct
Complication of reorganization of chronic pulmonary embolus
Pulmonary Hypertension
