Flashcards in Hemostasis and Related Disorders Deck (165)
What molecule mediates the transient vasoconstriction of primary hemostasis? What cell type releases this molecule?
What clotting factor binds subendothelial collagen?
Platelets bind vWF via what receptor?
What two molecules are contained within Weibel Palade bodies?
vWF and P-selectin
What is contained in dense granules? What cell type?
ADP and calcium
GpIIb/IIIa is upregulated on the surface of platelets by what signal?
ADP binding ADP receptor
What molecule binds to GpIIb/IIIa?
What are petechiae indicative of?
What is a normal platelet count? Below what level can lead to petechiae?
150 - 400
What isotype of immunoglobulin is produced during Immune Thrombocytopenia? Against what?
What cell type produces the Ab during Immune Thrombocytopenia? What organ is this cell located? What organ consumes these RBCs?
Acute Immune Thrombocytopenia arises in what patient population? After what two happenings?
viral infection or vaccination
Chronic Immune Thrombocytopenia arises in what patient population?
women of childbearing age
Are any coagulation factors affected during Immune Thrombocytopenia? Why?
no . only destruction of GpIIb/IIIa
What is the initial treatment of Immune Thrombocytopenia?
corticosteroids = initial Tx
What two reasons is a splenectomy used as treatment for Immune Thrombocytopenia?
removes source of auto-Ab (splenic plasma)
removes site of platelet destruction (splenic macrophages)
What is microangiopathic hemolytic anemia?
pathological formation of platelet microthrombi in small vessels
What cellular happening is seen during MAHA?
What are the two classic disorders that will produce Microangiopathic Hemolytic Anemia?
TTP and HUS
Lack of what enzyme causes TTP? What is the normal function of this enzyme?
What patient population most often develops auto-ADMATS13 Ab's?
What specifc bacterial strain produces HUS? Where is this strain found?
E. coli O157:H7
Does HUS cause renal or CNS defects?
Does TTP cause renal or CNS defects?
Are coagulation factors effected during HUS or TTP? What does this mean?
PT/PTT = normal
What cellular happening is observed during TTP/HUS?
What would be observed on a bone marrow biopsy of during TTP/HUS?
What are the two treatments of TTP and HUS?
plasmapheresis and corticosteroids
What is defective/absent during Bernard-Soulier syndrome? What is impaired?
adhesion = impaired
What two cellular happenings are seen during during Bernard-Soulier syndrome?
mild thrombocytopenia and enlarged platelets
What is defective during Glanzmann thrombasthenia? What is impaired?
aggregation = impaired
What activates factor VII?
What activates factor XII?
Defects in primary homeostasis manifest as what? Where?
skin and mucosal bleeding
nose bleeds (Epistaxis)
Defects in secondary homeostasis manifest as what two conditions?
deep tissue bleeding
rebleeding after surgical procedures
PT measures which arm of the coagulation cascade?
Which clotting factors does PT measure?
I (fibrinogen), two, five, seven and ten
PTT measures which arm of the coagulation cascade?
What is the mode of inheritance of hemophilia A?
What are of the coagulation cascade would be effected during hemophilia A?
What coagulation factor is absent during Hemophilia B?
What coagulation factor is most likely to develop an autoantibody against it? How would this be diagnosed?
PTT does not correct upon mixing with normal serum
Will PTT be corrected if a patient with Hemophilia A is given normal serum?
Will PTT be corrected if a patient with Coagulation Factor Inhibitor is given normal serum?
What two sites will bleed during vWF Disease?
skin and mucosa
What branch of the coagulation cascade will vWF Disease effect? Why?
vWF binds and protects factor eight
What drug is used to Dx vWF Disease? What is the MOA of this drug?
causes vWF to bind GpIb
What drug is used to Tx vWF Disease? What is the MOA of this drug?
desmopressin causes endothelial cells to release vWF from Weibel-Palade bodies
What factors are regenerated by Vitamin K?
two, seven, nine, ten, C and S
What branch of the coagulation cascade is used to follow liver failure?
What protein do platelets bind during HIT?
What isotype of Ab is involved during HIT?
What pro-coagulant is contained in amniotic fluid?
What two bacteria are the most common causes of septic DIC?
Why does sepsis cause DIC? Why?
influences endothelial cells to make tissue factor
What coagulation factor is tissue factor?
What type of neoplasia can result in DIC? What specific product causes this?
What type of leukemia can cause DIC? Why?
acute promyelocytic leukemia
What type of bite can cause DIC?
What is the serologic marker for DIC? What is D-Dimer derived from?
fibrin split products
What surgery can cause a disorder of fibrinolysis? Why?
release of urokinase
What if the function of urokinase?
Why can liver failure result with a defect in fibrinolysis?
decrease production of α2 anti-plasmin during liver failure
Why do errors in fibrinolysis produce an increase in PT and PTT?
plasmin degrades coagulation factors
Is the platelet count normal during errors of fibrinolysis?
What is the Tx of disorders of fibrinolysis? What is the MOA of this drug?
blocks activation of plasminogen
What is the histological pathological finding of thombosis? What are the three components?
Lines of Zahn
platelets and fibrin and RBCs
What is Virchows triad?
stasis, endothelial damage, hypercoaguable state
What two anti-coagulant molecules are produced by healthy endothelial cells?
PGI2 and NO
What fibrinolytic molecule is secreted by a healthy endothelium?
What are the three functions of plasmin?
1. cleave fibrin and fibrinogen
2. destroy coagulation factors
3. block platelet aggregation
Does thrombomodulin activate Protein C or does Protein C activate thromobomodulin?
thrombomodulin activates Protein C
What coagulation factors are destroyed by Actiated Protein C?
five and eight
Deficiency of what vitamin can lead to endothelial damage?
Deficiency of what enzyme can result in homocystinuria?
What are the four defects of CBS deficiency?
long slender fingers
Deficiency of what two proteins predispose to warfarin induced necrosis? Why?
Protein C or Protein S
C and S have shorter half-lifes than two, seven, nine or ten
Why does warfarin induced skin necrosis happen?
microthrombi form in vessels
Why does Factor V Leiden produce hypercoaguable states?
Factor V lacks cleavage site for APC
How is antithrombin deficiency diagnosed?
heparin does not produce increase in PTT
What type of drug is associated with an increase in coagulation factor synthesis?
What is the characteristic histological feature of emboli?
Fracture of what type of bones are indicative of a fat embolus?
What are the two gross manifestations of fat emboli?
petechiae on skin over chest
Pain from what two locations are characteristic of the bends?
joint and muscle
What happens to bones during Caisson disease?
multifocal ischemic necrosis of bone
Gestational emboli has what two histological components located inside of it?
What three veins does a PE most often arise from?
femoral, iliac and popliteal
What is elevated during a pulmonary embolism?
In what part of the heart do systemic emboli usually arise?
What is the first step of primary hemostasis?
What cell synthesizes TXA2 during the clottign cascade?
What organ is the most at risk of bleeding during severe thrombocytopenia?
What is a normal bleeding time?
Which immunoglobulin can cross the placenta?
What cell undergoes hyperplasia during Immune Thrombocytopenia? Where?
on bone marrow biopsy
What is the secondary Tx of immune thrombocytopenia?
IV immunoglobulin = secondary
gives splenic macrophages something to chew on rather than IgG anti-GpIIb/IIIa
What cell is depleted during Microangiopathic Hemolytic Anemia?
Where is E. coli O157:H7 found?
What cell type is damaged that leads to HUS?
Other than HUS, what can E. coli O157:H7 cause? What specific toxin?
What is the mnemonic to remeber the five clinical finding of TTP and HUS?
What does the C of CRSMF stand for?
What does the R of CRSMF stand for?
What does the S of CRSMF stand for?
skin and mucosal bleeding
What does the M of CRSMF stand for?
Microangiopathic hemolytic uremia
What does the F of CRSMF stand for?
Why does TTP and HUS cause skin and mucosal bleeding?
low platelets due to microthrombi formation
What myeloid cell would increase in number on a PBS during TTP or HUS?
Why are corticosteroids used to treat TTP?
corticosteroids decrease number of antibody producing cells
What do platelets look like in Bernard-Soulier syndrome?
What drug can expose Glanzmann-Thrombasthenia? Why?
lack of TXA2 prevents aggregation
What cell contributes the phospholipid surface to the coagulation cascade?
What two locations body does a patient with Hemophilia A present with bleeding?
What is the treatment for Hemophilia A?
Recombinant Factor 8
How does von Willebrand Disease typically present?
mucosal and skin bleeding
What is the most common disorder of coagulation?
What coagulation factor does vWF bind to and stabilize?
Regarding coagulation, what specific chemical reaction does Vitamin K catalyze?
Regarding coagulation, what enzyme is located in the lilver?
Vitamin K epoxide reductase
What is the feared result of HIT?
What are the two common bleeding sites of DIS?
Regarding DIC, what in amniotic fluid can activate the coagulation cascade?
What specific type of cancer can cause DIC? Why?
acute promyelocytic leukemia
expansion of platelets and their release of primary granules
What type of histological feature is present in Acute Promyelocytic Leukemia?
What is the Tx for DIC? What is contained in this?
What protein inactivates plasmin?
What factor is used to differentiate a disorder of fibrinolysis vs. DIC?
fibrinolysis disorder = normal platelet count
DIC = low platelets
What cell type produces anti-Thrombin III?
What cell type produces tPA?
What cell type produces thrombomodulin?
What are the three causes of endothelial damage?
atherosclerosis, vasculitis, high serum homocysteine
Initial warfarin therapy results in a deficiency of what two anti-coagulants?
Protein C and Protein S
What is the mutated version of prothrombin? What mutation is present?
What is the key histological fidning of an atherosclerotic embolus?
What is the chronic form of a gas embolus?
What is Caissons disease characterized by?
multifocal ischemic necrosis of bone
What is the main complication of chronic pulmonary emboli?
How can anemia present in an individual with already poor coronary vascular function?
Where in the GI tract does absorption of ironn occur?
What is contained within α-granules of platelets?
vWF and fibrinogen
Why can oral contraceptives result in a hypercoaguable state?
estrogen promotes synthesis of clotting factors
What type of neoplasia can cause iron deficient anemia?
What is the most common cause of a decrease in ADAMTS13?
Would a disorder of fibrinolysis present with D-dimers? Why or why not?
decreased fibrinolysis only--> no degradation of D-dimers to begin with
What is lysed during a disorder of fibrinolysis?
What is the most common cause of thrombocytopenia in children and adults?
What is the most common inherited coagulation disorder?
Bernard soulier disease
Why does Prothrombin 20210A result in a hyper-coaguable state?
too high of levels of prothrombin
Which granule of platelets is vWF contained?
What is a normal bleeding time?
Which myeloid cell does uremia interrupt?
Which four clotting factors does the PT follow?
PTT follows all factors except which two?
seven and thirteen
Does HIT produce a hypocoaguable or hypercoaguable state?
Which two cytokines are involved during DIC? Via wat mechanism?
TNF and IL1
induce endothelial cells to release tissue factor
Does use of lytics increase or decrease BT?
Which cell type synthesizes AT III?
What does plasmin do to platelets?
blocks their aggregation
Which cell type secretes tPA?
What gets transferred from THF to B12? What is the fate of this molecule?
homocysteine to methionine
Is GpIb involved with adhesion or aggregation?
Is GpIIb/IIIa involved with adhesion or aggregation?
What is the key difference between DIC and disorders of fibrinolysis?
no D-dimer with fibrinolysis problems