Chapter 4 ( Hemostasis ) Flashcards by Ahmed Safwat

In primary hemostasis , transient vasoconstriction of the blood vessel mediated by what ?

1- reflex neural stimulation

2- Endothelin released from endothelial cells

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Von Willebrand factor function ? Source ?

Derived from the Webel-Palade bodies of endothelial cells and alpha-granules of platelets
Responsible for the platelet adhesion to vessel wall in primary hemostasis by binding :
1- exposed subendothelial collagen
2- GPIb receptor on the platelet

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Mechanism of platelet degranulation in primary hemostasis ? Mediators released ?

Adhesion induces shape changes in the platelets and degranulation with release of these mediators :
1- ADP from platelet dense granules which promote exposure of GPIIb/IIIa receptor on the platelet
2- TXA2 which promotes platelet aggregation

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Mechanism of platelet aggregation in primary hemostasis ?

By GBIIb/IIIa using fibrinogen as a linking molecule

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Petechiae , purpura , ecchymosis sizes ?

Petechiae : 1-2 mm
Purpura : 3-10 mm
Ecchymosis : > 1 cm

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Petechiae is a sign of ?

Thrombocytopenia and not usually seen with qualitative disorders

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Bleeding time

2-7 mins

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Mechanism of ITP ?

Autoimmune production of IgG ( produced by plasma cells of spleen )against platelet antigens

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Lab findings of ITP ?

Decreased platelet count
Normal PT/PTT
Increased megakaryocytes on bone marrow biopsy

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Mechanism of microangiopathic hemolytic anemia ?

Pathologic formation of platelet microthrombi in small blood vessels results in :
1- consumption of platelet
2- RBCs are sheared as they dross the microthrombi resulting in hemolytic anemia with Schistocytes

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Microangiopathic hemolytic anemia is seen in which disease ?

TTP

HUS

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Mechanism of TTP ?

Decrease of ADAMTS13 ( usually by an acquired autoantibody , which normally cleaves vWF multimers into smaller monomers for eventual degradation , large uncleaved multimers lead to abnormal platelet adhesion resulting in microthrombi

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HUS mechanism ?

Endothelia damage by drugs or infection

Ex : children with E coli O157:H7 dysentery , E coli verotoxin damage endothelial cells

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Clinical findings of TTP and HUS ?

1- skin and mucosal bleeding 
2- MHA
3- Fever 
4- renal insufficiency 
5- CNS abnormalities

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Lab findings of MHA ?

Decreased platelet count 
Increased bleeding time 
Normal PT / PTT
Anemia with schistocytes 
Increased megakaryocytes on bone marrow biopsy

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Bernard Soulier syndrome defect ? Findings ?

GPIb deficiency so platelet adhesion is impaired

Big platelets Sucked platelet number

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Glanzmann thrombasthenia defect ?

GPIIb/IIIa deficiency resulting in impaired platelet aggregation

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How aspirin decrease platelet aggregation ?

By inactivating cyclooxygenase leads to TXA2 deficiency

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Mechanism of stabilization of the weak platelet plug in secondary hemostasis ?

Coagulation cascade generates Thrombin —> converts fibrinogen into fibrin —> fibrin is then cross-linked —> stable platelet fibrin thrombus

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Activation of factors of coagulation cascade requires what ?

1- exposure to an activating substance :
Tissue thromboplastin activates factor Vll
Subendothelial collagen activates factor Xll
2- phospholipid surface of the platelet
3- calcium ( from platelet dense granules )

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Lab findings in hemophilia A ?

Increased PTT
Norma PT
Decreased factor Vlll
Normal platelet count 
Normal bleeding time

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Hemophilia B ( Christmas disease ) defect ?

Factor lX deficiency

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Coagulation factor inhibitor defect ? DD with hemophilia A ?

Acquired antibody against a coagulation factor , anti Factor Vlll is most common
PTT doesn’t correct upon mixing normal plasma with patient’s plasma ( contrary to hemophilia A )

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Most common inherited coagulation disorder ?

Von Willebraand disease

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Lab findings of Von Willebraand disease ?

Increased bleeding time Increased PTT ( vWF normally stabilize factor Vlll ) Normal PT Abnormal Ristocetin test

Ristocetin action ?

Induces platelet agglutination by causin vWF to bind platelet GPlb

Ttt of Von Willebraand disease

Desmopressin | Which increases vWF release from Weible Palade bodies of endothelial cells

Enzyme that activate Vitamin K in the liver ?

Epoxide reductase

Effect of liver failure on coagulation is followed by ?

Causes of DIC ? Their mechanisms ?

1- obstetric complications : Tissue thromboplastin in amniotic fluid activates coagulation 2- sepsis : Endotoxins and cytokine ( TNF , IL1 ) induce endothelial cells to make tissue factor 3- adenocarcinoma : Mucin activates coagulation 4- acute promyelocytic leukemia : primary granules activates coagulation 5- rattlesnake bite : venom activates coagulation

Lab findings of DIC ?

``` Decreased platelets Increased PT /PTT Decreased fibrinogen Microangiopathic anemia Elevated D dimer ```

The best screening for DIC ?

Elevated D dimer

Source of D dimer ?

Splitting of cross linked fibrin , not from splitting of fibrinogen

Mechanism of heparin induced thrombocytopenia ?

Heparin can form a complex with a molecule on the surface of platelets called platelet factor 4 to which the patient’s immune system form an IgG autoantibodies leading to consumption of the platelets by spleen , fragments of destroyed platelets may activate the remaining platelets to form thrombi

Functions of plasmin ?

1- cleaves fibrin and serum fibrinogen 2- destroys coagulation factor 3- blocks platelets aggregation

Enzymes that inactivates plasmin ?

Alpha2-antiplasmin

Causes of abnormal increase in fibrinolysis ? Their mechanisms ?

1- radical prostatectomy : release Urokinase that activates plasmin 2- cirrhosis of liver : reduces the production of alpha2-antiplasmin

Lab findings of increased fibrinolysis ?

Increased PT / PTT Increased bleeding time Normal platelet count Normal D dimer

Ttt of increased fibrinolysis ?

Aminocaproic acid : blocks activation of plasminogen

Features that distinguish thrombus from postmortum clot ?

1- lines of Zahn | 2- attachment to vessel wall

Causes for disruption of normal blood flow ?

Immobilization Cardiac wall dysfunction Aneurysm

Role of endothelia cells in preventing thrombosis ?

``` 1- block exposure of subendothelial collagen and underlying tissue factor 2- produces Prostacyclin PGI2 and NO 3- secrete heparin-like molecules 4- secrete tissue plasminogen activator 5- secrete thrombomodulin ```

Function of thrombomodulin ?

Redirects thrombin to activate protein C

Causes of endothelia cells damage ?

Atherosclerosis Thrombosis Homocysteinemia

Protein C and S functions ?

Inactivates factors V , Vlll

Mode of inheritance of protein C and S deficiency ?

Autosomal dominant

Factor V Leiden ?

Mutated form of factor V , that lacks the cleavage site for deactivation by protein C and S

Most common inherited cause of hypercoagulable state ?

Factor V Leiden

Prothrombin 20210A ?

Inherited point mutation in prothrombin that results in increased gene expression

Anti-thrombin lll deficiency mechanism ?

Decrease the protective effect of heparin like molecules produced by the endothelium —> increase risk of thrombosis

Key diagnostic feature of Anti-thrombin lll deficiency ?

PTT doesn’t rise with standard heparin dosing

Ttt of anti-thrombin lll deficiency ?

High doses of heparin to activate the limited anti-thrombin lll , coumadin is then given to maintain an anticoagualble state

Mechanism of oral contraceptives in causing hypercoagulable state ?

Estrogen induces increased production of coagulation factors

Characteristic of atherosclerotic embolus ?

Presence of cholesterol clefts in the embolus

Fat embolus clinical features ?

Dyspnea | Petechiae on the skin overlying the chest

Decompression sickness clinical features ?

``` Joint and muscle pain ( bends ) Respiratory symptoms ( chokes ) ```

Chronic form of decompression sickness ( gas embolus ) ? Characteristic ?

Caisson disease | Multifocal ischemic necrosis of bones

Amniotic fluid embolus clinical features ? Characteristic ?

Dyspnea Neurologic symptoms DIC Presence of Squamous cell and keratin debris from fetal skin in embolus

Why pulmonary embolism is most often silent ?

Dual blood supply of the lung | The embolus is usually small

Gross examination of pulmonary embolism ?

Hemorrhagic wedge shaped infarct

Cause of death in pulmonary embolism ?

Electromechanical dissociation