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Flashcards in Hemostasis Deck (68):

Primary Hemostasis

Forms a weak platelet plug. Mediated by interaction between platelets with vessel wall


Secondary Hemostasis

Stabilize platelet plug and mediated by coagulation cascade. Coagulation cascade generates thrombin which converts fibrinogen in paltelet plus to mroe stable fibrin. Fibrin is then crosslinked ot make even stronger.


Steps of Primary Hemostasis

1) Transient vasoconstriction of damaged vessel via neuroal stimulation and endothelin release from endothelial cells
2) Platelet adhesion to disrcupted vessel= Exposed subendothelial collagen binds vWF in plasma. Platelets bind to vWF via GPIb receptor. (vWF comes from Weibel Palade bodies of endothelial cells and alpa granules of platelets)
3) Platelet Degranulation = Platelets release ADP (promotes platelets to expose GPIIb/IIIa receptors on platelets) and Thromboxane2 (TXA2 promotes platelet aggregation)
4) Platelet Aggregation = Platelets cross-link to one another via GPIIb/IIIa's attaching to fibrinogen.
All results in a weak platelet plug that will be strengthened by coagulation cascade.


Disorders of Primary Hemostasis Quantitative vs Qualitative

Due to abnormalities with platelets. Quantitative = not enough platelets Qualitative = normal platelet counts but they do not function properly.


Clinical features of disorder of primary hemostasis

1)Mucosal bleeding = epistaxis (nose bleed), hemoptysis (cough blood), GI bleed, hematuria, menorrhagia, if severe intracranial bleeding
2) Skin Bleeding = petechia ->purpura->ecchymoses and easy brusing. Petechia usually sign of throbocytopenia (quantitative problem not qualitative)



pinpoint bleeds. Usually sign of thrombocytopenia (quantitative not qualitative)


Weibel Bodies

Found in endothelial cells. Produce vWF and P-selectin (used as speed bump for rolling)


Normal Lab values for
1) Platelet Count
2) Bleeding time
3) Blood Smear
4)Bone Marrow Biopsy

1) Platelet Count = 150,000-400,000
2) Bleeding time = 2-7mins
3) Blood Smear = estimate number of platelets and size/shape
4)Bone Marrow Biopsy = asses megakaryocytes (they produce platelets. If they are big or too many then indicates that body is trying to adapt to thrombocytopenia


Immune Thrombocytopenic Purpura (ITP)

Autimmune production of IgG platelets against platelet antigens (GPIIb/IIIa) and is most common cause of thrombocytopenia. Spleen makes the IgG and then also site of destruction of platelets with attached IgG.
Lab = decreased platelets, Normal PT/PTT (coagulation factos not affected), Increase in megakaryocytes
Treat with IVIG (trick spleen to eat these Ig and leave platelet tagged Ig alone = shortlived) or with corticosteroids.
Splenectomy eliminates source of antibody and destruction


Acute vs Chronic ITP

ITP = Immune Thrombocytopenic Purpura
Acute = seen in children after viral infection or immunization. Self limiting
Chronic = adults, usually women of childbearing age. Can be primary of unknown origin or secondary to autoimmune diseas like SLE. Pregnant mom can have thrombocytopenic child since IgG can cross placenta and mark childs platelets for destruction but will be self limiting attack once child is born


Microangiopathic Hemolytic Anemia

Pathologic platelet microthrombi in small vessels. Platelets are depleted in forming many microthrombi and they form jagged edges that shear RBCs resulting in hemolytic anemia with characterisitic shistocytes (appear as "helmet cells" or cells with two points)
2 examples are Thrombocytopenic Purpura and Hemolytic Uremic Syndrome


Thrombocytopenic Purpura (TTP)

Microangiopathic Hemolytic Anemia due to decreased ADAMTS13 which is an enzyme that typically cleaves vWF multimers. Large vWF multimers lead to abnormal platelet adhesion = microthrombi.
ADAMTS13 usually decreased due to acquired autoantibody (especially in adult females)


Hemolytic Uremic Syndrome (HUS)

Microangiopathic Hemolytic Anemia due to endothelial damage by drugs or infection. Tyically seen in E Coli O15:H7. Get E coli from undercooked beef and release verotoxin that damage endothelial cells resulting in platelet microthrombi. Also get E coli O15:H7 dysentery - mucusy diarrhea. Damage typically occurs in kidney so also get a resultant uremia


Clinical and Lab Findings in HUS and TTP

Hemolytic Uremic Syndrome (HUS) and Thrombocytopenic Purpura (TTP) are Microangiopathic Hemolytic Anemias. See skin and mucosal bleeding, fever, renal insufficiency (especially HUS) and CNS abnormalities (especially TTP)
Lab: thrombocytopenia w/ increased bleeding time, normal PT/PTT, anmia with schistocytes, increase in megakaryocytes


Bernard-Soulier Syndrome

Genetic GPIb deficiency. vWF attatches to collagen as normal but platelets lack GPIb to attach to vWF and get no platelet adhesion. See mild thrombocytopenia (defective platelets destroyed sooner) and enlagred platelets


Glanzmann Thrombasthenia

Genetic GPIIb/IIIa deficiency so platelet aggregation is impaired


Effect of Aspirin on Platelets

Aspiring irreversibly inactivates cyclooxygenase so get a lack of TXA2 and therefore reduced signaling for platelets to aggregate


Uremia effect on Platelets

Impairs platelet adhesion and aggregation


Production and activation of Coagulation factors

Made in an inactive form in the liver. Activated via extrinsic (tissue thromboplastin activates factor VII) and intrinsic (subendothelial collagen activates factor XII) as well as the phospholipid surface of platelets and calcium from paltelet granules. Need all three to be activated.


Clinical Features of Disorders of Secondary Hemostasis

Deep tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures


Laboratory Features of Secondary Hemostasis

Prothrombin time measures extrinsic (factor VII) and common (factors II, V, X)
Partial thromboplastin time measures intrinsic (factors XII, XI, IX, VIII) and common (factors II, V, X)


Intrinsic vs Extrinsic pathway

Intrinsic = SEC(subendothelial collagen), XII, XI, IX, VIII, X, V, II, I = measured by PTT, and measures HEParin
Extrinsic = TT(tissue thromboplastin) VII, X, V, II, I = measured by PT, measures coumadin


Hemophilia A

Genetic factor VIII deficiency (problems with intrinsic pathway). X-linked recessive(mostly males) although de novo mutations do occur.
Present with deep tissue, joint, and postsurgical bleeding
Labs = Increased PTT, normal PT, normal platelet and bleeding time.
Treat with recombinant VIII


Hemophila B (Chirstmas disease)

Factor IX Deficiency (problems with intrinsic pathway)
Present with deep tissue, joint, and postsurgical bleeding
Labs = Increased PTT, normal PT, normal platelet and bleeding time.
Treat with recombinant IX


Coagulation Factor Inhibitor

Acquired antibody against a coagulation factor resulting in impaired function. anti FVIII most common.
Present with deep tissue, joint, and postsurgical bleeding
Labs = Increased PTT, normal PT, normal platelet and bleeding time.
PTT does not correct upon mixing with normal plasma with patients plasma (mixing study)


Mixing Study

Mix patients plasma with normal plasma. If hemophilia then PTT should correct once it is exposed to VIII in normal plasma. PTT will not correct in Coagulation factor inhibitor cus inhibitor will still be present in patient's plasma and affect normal plasma.


Von Willebrand Disease

Genetic vWF deficiency is most common inherited coagulation disorder. Multiple subytypes exist (both qualitative and quantitative) but most common is autosomal dominant with decreased vWF levels.
Presents with mdoerate mucosal ad skin bleeding since low vWF impairs platelet adhesion.
Labs: increased bleeding time, increased PTT, normal PT(vWF normally stabilizes VIII)
Deep tissue, joint, and postsurgical bleeding are not seen.
Abnormal Ristocetin test = ristocetin normally induces platelet aggutination by causing vWF to bind platelet GPIb but since no vWF get abnormal test.
Treat with desmopressin (ADH analog) which increases vWF production from Weibel-Palade bodies of endothelial cells


Ristocetin test t

ristocetin normally induces platelet aggutination by causing vWF to bind platelet GPIb but if no vWF get abnormal test


desmopressin (ADH analog)

increases vWF production from Weibel-Palade bodies of endothelial cells. Treat vWF disease


Vitamin K

Activated by expoxide reductase (blocked by coumadin).
Typically gamma carboxylates factors II, VII, IX, X, and proteins C and S.
Typically produced by bacteria in GI


Vitamin K Deficiency

Disrupts multiple coagulation factors. Occurs in
1)newborns-due to lack of GI colonization by bacteria. Give prophylactic vitamin K shot
2) Long term antibiotic therapy - kills vitamin k producing bacteria
3) Malabsorption - cant digest fat soluable vitamins including Vitamin K


Liver Failure

Decreased production of coagulation factors and decreased activation of vitamin k by epoxide reductase. Follow using PT


Large Volume Transfusion

Dilutes coagulation factors resulting in a relative deficiency


Heparin Induced Thrombocytopenia

Heparin forms complex with PF4 of platelets, patient develops IgG against this complex and "tagged" platelets are subsequently destroyed by spleen.
Fragments of destroyed platelets may activate remaining platelets, leading to thrombosis


Disseminated Intravascular Coagulation

Pathologic activation of the coagulation cascade leads to widespread microthrombi (ischemia and infarction) and consumption of platelets results in excessive bleeding at IV sites and mucosal surfaces. Almost always secondary to another disease process


Disease Processes that can cause Disseminated Intravascular Coagulation

1) Obstetric Complication - tissue thromboplastin in amniotic fluid activates coagulation
2) Sepsis (E coli or N meningitidis) = endotoxins from bacterial wall and cytokines (TNF and IL-1) induce endothelial cells to make tissue factor
3) Adenocarcinoma = mucin activates coagulation
4) Acute Promyelotic leukemia = primary granules activate coagulation
5) Rattlesnake bite = venom activates coagulation


Laboratory Findings of DIC

Decreased platelet count, increased PT/PTT, decreased fibrinogen, microangiopathic hemolytic anemia, elevated fibrin split product (D DIMER!!!!)


D Dimer

Best screening for DIC. Derived from splitting of cross linked fibrin.



Removes thrombus after after damaged vessel heals. tissue Plasminogen Activator (tPA) converts plasminogen to plasmin. Plasmin cleaves fibrin and serum fibrinogen, destroys coagulation factors, and blocks platelet aggregation. Plasmin is inactivated by alpa2 antiplasmin.



tissue Plasminogen Activator (tPA) converts plasminogen to plasmin. Plasmin cleaves ferum and serum fibrinogen, destroys coagulation factors, and blocks platelet aggregation. Plasmin is inactivated by alpa2 antiplasmin.


Disorder of Fibrinolysis

Plasmin overactivity results in excessive cleavage of serum fibrinogen. Includes
1)Radical Prostatectomy - release of urokinase activates plasmin
2) cirrhosis of liver - reduced production of alpha2-antiplasmin
Present with increased bleeding that resembles DIC.
See increased PT/PTT (coagulation factors destroyed), increased bleeding time with normal platelet count, and increased fibrinogen split products without D-Dimers
Treat with aminocaproic acid



Pathological formation of intravascular blood clot.
Occurs in A or V and most commonly seen as DVT below the knee
Distinguished from post mortem clot by lines of zahn (alternating layers of platelets/fibrin and RBCs) and attachemnet to vessel wall
Risk factors are 1)disruption in blood flow 2) endothelial cell damage 3)hypercoaguable state


Virchows Triad

Increase chance of thrombosis
1) disruption in blood flow
2) endothelial cell damage
3) hypercoaguable state


Disruption in Blood Flow

Increases chance of thrombus
Stasis and turbulence (normally laminar flow) allows blood to slow down and be more likely to clot
Immobilization after a surgery
Cardiac wall dyfunction = arrythmia or MI
Aneurysm = balloning of vessels introduces turbulent flow and disrupts laminar flow


How Endothelial cells normally protect from thrombus

1) Block exposure to subendothelial collagen and underlying tissue factor
2) Produce prostacyclin (PGI2) and NO that vasodilate and inhibit platelet aggregation
3) Secrete heparin like molecules = augment antithrombin III (ATIII) which inactivates thrombin and coagulation factors
4) secrete tPA = converts plasminogen to plasmin which goes on to cleave fibrin and fibrinogen, destroy coagulation factors, and block platelet aggregation
5)secrete throbomodulin = redirects thrombin to activate protein C which inactivates factors V and VII


prostacyclin (PGI2) and NO

Produced by endothelial cells. vasodilate and inhibit platelet aggregation


augment antithrombin III (ATIII)

Produced by endothelial cells and Inactivates thrombin and coagulation factors



Secreted by endothelial cells and converts plasminogen to plasmin which goes on to cleave fibrin and fibrinogen, destroy coagulation factors, and block platelet aggregation



Endothelial cells secrete throbomodulin and it redirects thrombin to activate protein C which inactivates factors V and VII


Causes of Endothelial cell damage

1) atherosclerosis
2) vasculitis
3) high levels of homocysteine


Vitamin B12 and Folate Deficiency

Results in mildly elevated homocysteine levels that damages endothelial cells
Folic acid circulates as methyl-THF -> it trasnfers its methyl to B12 (cobalmin) so it can go and help in DNA synthesis-> B12 (cobalmin) transfers methyl to homocysteine converting it to methionine. If lack Folic acid or B12 then lose this process and get buildup of homocysteine


Cystathionine Beta Sythase Deficiency

CBS normally converts homocysteine to cystathionine so deficiency increases homocysteine and damages endothelial cells.
Get vessel thrombosis, mental retardation, lens dislocation, and long slender fingers


Hypercoaguable State

Due to excessive procoagulant proteins or defective anticoagulant proteins. Classicaly presents as reccuring or early age DVT


Protein C or S deficiency

C and S normally inactivate factors V and VII, so if missing get increase in these factos and hypercoaguable


Warfarin Skin Necrosis

Increased risk for thrombosis, especially in the skin, when have a defiency in proteins C and S and treated with warfarin.
Warfarin eliminates production of coagulation factors II, VII, IX, X, and proteins C and S. But C and S have shorter half life so the ydissapear first so there is a window where person on warfarin is actually hypercoaguable. Thats why we normally treat with Heparin until this window has passed


Factor V Leiden

Mutated form of Factor V that lacks cleavage site for C and S to act on leading to hypercoaguability.
Most common inherited hypercoaguable state


Prothrombin 20210A

Inherited point mutation in prothrombin results in overexpression. Results in increased prothrombin->thrombin-> promotes thrombus formation


ATIII Deficiency

Defieincy decreases effects of heparin like molecules from endothelial cells and makes thrombus more likely. ATIII is normally activated by heparin like factorsand goes on to inactivate thrombin and coagulation factors.

In AIII deficiency, treatment with heparin does not raise PTT. Have to give a extremely high dose and give with coumadin


Oral contraceptives

Estrogen increases production of coagulation factors and increases risk for thrombosis



Intravascualr mass that travels and occludes downstream vessels. SYmptoms depend on vessel occluded



Thrombus that dislodges. Most common >95%


Atherosclerotic embolus

Throbums that dislodges


Fay embolus

assoicated with bone fractures and soft tissue trauma. Characterized by dyspnea and pethechia over chest wall


Gas embolus

Classically see in divers that ascend too fast and have nN2 form and get bends =pain in joints and muscles
Can also occur after laprascopic surgery


Caisson Disease

Multifocal ischemic necrosis of bone due to chornic gas embolism


Amniotic Fluid embolus

embolus enters maternal circulation during delivery.
Classicaly pressents with dyspnea, neuro symptoms, and DIC


Pulmonary Embolism

Usually due to thromboembolus. 90% of the time it is clinically silent becuase lung has dual blood supply and embolus is very small.
Pulmonary infarction can occur if throbus blocks a larger artery and there is a preexisting cardiopulmonary compromise. = presents with dyspnea, hemoptysis, pleurtitic chest pain, and pleural effusion. Also so perfusion is abnormal, detect DVT by ultrasound, D dimers are elevated, and a wedge shaped infarct of the lung

Chronic PE can cause pulmonary hypertension.


Saddle Embolus

Embolus that is large enough to block both left and right ppulmonary arteries or significant occlusion of large pulmonary artery. Leads to death