Flashcards in Coagulation Part II Deck (62):
How do you initially manage thrombocytopenia?
If platelets are below 10,000 you must treat immediately. Use corticosteroids (to stabilize the vessel wall; only works transiently).
Emergency therapy= platelet transfusions, IV IgG, IV anti-Rh(D).
What are the 2 causes for low platelet counts?
1. lack of production
2. increased peripheral destruction
What produces platelets?
megakaryocytes produced from the bone marrow. They have a lifespan of 7 days once released from the bone marrow. They are then removed by the spleen liver and lymph nodes.
How does IV IgG and IV anti-Rh(D) work?
they inhibit the removal of platelets
What is the first thing you want to rule out if you think you are dealing with thrombocytopenia?
pseudothrombocytopenia= false-positive result that may occur when automated platelet counting devices are used.
To rule this out, you must look at the peripheral blood smear to look for platelet clumps.
With what is pseudothrombocytopenia associated?
the use of ethylenediaminetetraacetic acid (EDTA) as an anticoagulant, platelet cold agglutinins, and multiple myeloma.
What diseases may cause a secondary thrombocytopenia?
- bone marrow aplasia
If you can not diagnose any of the diseases that can cause thrombocytopenia, what are the 2 diagnoses of exclusion that could be causing it?
1. idiopathic thrombocytopenic purpura (ITP)
2. drug-induced thrombocytopenia
What are some medications that can cause immune thrombocytopenia?
quinine and quinidine, heparin, sulfonamides, antibiotics...
What are some medications that can suppress platelet production?
ethanol, thiazide diuretics, and cancer chemotherapeutic agents
What is idiopathic thrombocytopenic purpura (ITP)?
an autoimmune increased peripheral platelet destruction. It impairs megakaryocyte maturation and platelet production.
How do we manage ITP?
- discontinue medications that could cause it and administer Rituximab (anti-CD20).
- If this fails a splenectomy may be performed.
- May also use danazol, immunotherapy, or thrombopoietin mimicking agents to stimulate platelet production if refractory thrombocytopenia occurs.
How is ITP related to children?
it is associated with vaccinations, but usually does not require medications (avoid corticosteroids bc it will affect growth).
Do most women during pregnancy become thrombocytopenic?
YES, but normally it is ok. The only time we intervene is if the platelet count drops below 100,000.
What are some common acquired platelet disorders?
- aspirin and anti-platelet drugs
- uremia (high level of waste products in the blood due to renal failure).
- liver disease
- cardiopulmonary bypass
What is Bernard-Soulier syndrome?
defect in platelet plug formation (primary hemostasis) and will see very large platelets. Decreased GpIb causes defect in platelet-to-vWF adhesion.
* Note in vWD the defect is in vWF (but same problem occurs).
What is Glanzmann thrombasthenia?
defect in platelet plug formation (primary hemostasis). Decreased GpIIb/IIIa causes defect in platelet-to-platelet aggregation.
Will there be agglutination on ristocetin cofactor assay if you have Bernard-Soulier syndrome?
NO, because ristocetin requires vWF to clump, and it is not present here.
Will there be agglutination on ristocetin cofactor assay if you have Glanzmann thrombasthenia?
YES! Blood smear shows platelet clumping, because ristocetin requires vWF to clump.
What do platelets do following attachment to vWF on the endothelium?
secrete ADP and serotonin (from their dense bodies) and proteins (from their alpha granules).
What is storage pool disease?
deficiency in platelet dense bodies, and therefore they cannot secrete ADP and serotonin.
*most common platelet hereditary disorder
What is Gray Platelet syndrome?
deficiency in alpha granules, and therefore they cannot secrete platelet specific proteins.
What follows secretion of ADP, serotonin, and proteins from the platelets?
aggregation via GpIIb/IIIa receptor and fibrinogen (which binds to this receptor).
What is Scott's syndrome?
defect in the platelet membrane (factors 5 and 10) during coagulation (secondary hemostasis).
What 3 things cause platelet adhesion and activation?
2. shear stress
* These lead to the release of serotonin, ADP, and proteins from the granules.
How does Aspirin work?
it blocks cycloocygenase-1 and 2 irreversiby, preventing the synthesis of thromboxane A2 (TXA2= potent vasoconstrictor and promotes platelet clotting).
How do Abciximab and Eptifibatide work?
they block GpIIb/IIIa and thus platelet aggregation
How does clopidogrel (plavix) work?
inhibits ADP receptor P2Y, thus inhibiting platelet aggregation
How do you diagnose platelet dysfunction?
history of mucosal bleeding, bruising, and increase bleeding time on lab tests. May also see petechiae.
How do you manage pts with platelet dysfunctions?
discontinue use of aspirin, give DDAVP if they have uremia, and manage underlying condition.
What are some risk factors for venous thrombotic events?
malignancy, surgery, trauma, infections, age and immobilization, pregnancy, oral contraceptives, and hormone replacement therapy.
Also anti-phospholipid syndromes, thrombophilia, and medications like asparaginase
What are anti-phospholipid syndromes (APS)?
antibodies against phospholipids of endothelial cells and many other cells.
What is primary APS?
occurs in patients with SLE
What is secondary APS?
occurs in patients with infections (HIV, hepatitis C...), medications, and those who have a genetic predisposition
What should lead you to suspect a patient has an anti-phospholipid syndrome?
- history of miscarriages, recurrent thrombosis, unexplained stroke, dementia, or visual changes.
- prolonged PTT but no abnormal bleeding (because the problem is thrombosis).
- abnormal mixing studies
How do you diagnose APS?
- coagulation tests (cannot be done in anticoagulated pts).
- immunological tests= test for cardiolipin antibody (phospholipid).
What are the body's natural mechanisms for preventing coagulation?
- tissue factor pathway inhibitor (prevents factor 7 from forming factor 9).
- antithrombin III
- fibrinogenolysis and fibrinolysis
- thrombomodulin on the vessel wall will activate protein C (protein S is a cofactor for protein C), which inactivates factor 5.
What is factor 5 Leiden?
mutation of factor 5 that causes it to be resistant to degradation by activated protein C, leading to hypercoagulability. Pts have increased risk for blood clots, recurrent DVT and thromboembolism.
*#1 clotting disorder in caucasians
Is the prevalence of an antithrombin III, protein c or portein s deficiency high or low?
VERY LOW, but if you have it your likelihood of developing a thrombosis is high.
What are some clues for an underlying thrombophilia?
FX of venous thrombotic events, thrombosis in unusual locations (cerebral, hepatic, mesenteric or renal veins), and miscarriages
What is an indication for long term anticoagulation?
recurrent thrombosis (provoked or unprovoked).
-provoked= thrombus associated with a predisposing risk factor
-unprovoked= thrombosis without a risk factor (idiopathic)
Is long term anticoagulation indicated for a patient with thrombophilia with no history of thrombosis?
Can you give warfarin (coumadin) to a pregnant mother?
NO because it can cross the placental barrier and be transmitted through breast milk. You can use low molecular weight heparin however.
Do mothers have a higher or lower incidence of a venous thromboembolism during postpartum or antepartum period?
Can you give heparin out of the hospital?
NO because it is only given IV. You can give low molecular weight heparin however outside of the hospital.
What are the direct thrombin inhibitors?
Argatroban and dabigatran. These are used to reverse heparin induced thrombocytopenia= paradoxical thrombosis from thrombocytopenia. Must be careful with these because they can really cause a lot of bleeding.
** If a pt has a history of abnormal bleeding, but normal PTT, PT, CBC, and platelets, what do they likely have?
either vWD or factor 13 deficiency (because factor 13 is not picked up in the bleeding time tests).
** If a pt does not have a history of abnormal bleeding, but their PTT= 90 sec (markedly abnormal), but a normal PT, what deficiency do they likely have?
Factor 11 (can live normal life with deficiency in this) or Factor 12 (deficiency does not cause physiological problems) deficiency.
** Do antibiotics cause a greater than expected INR?
YES because they may reduce some bacteria that produce vitamin K, which is necessary for blood coagulation. Thus, their bleeding time will be augmented.
** True or False: vWF binds to and protects factor 8, its activity is assayed by Ristocetin, and binds to GPIb receptor on platelet surface.
** If vWF activity/ vWF antigen ratio is less than 0.7, is this concordant or discordant?
CONCORDANT= type 1 vWD
** What is characteristic in TTP but not in DIC?
d-Dimers are not present in TTP. You treat with plasmapheresis.
** Is hemolytic anemia pressent in both TTP and DIC?
** What is DDVP used to treat?
Factor 8 deficiency (hemophilia A) and vWD
** Hemarthrosis, delayed bleeding, and x-linked recessive inheritance are characteristic of what disorders?
Factor 8 deficiency (hemophilia A) and factor 9 deficiency (hemophilia B)
** What is GpII/IIIa?
fibrinogen receptor and mediates platelet aggregation
** What is the initial management of ITP?
corticosteroids and withhold medications
** If the PTT is significantly increased in a patient with an anti-phospholipid antibody syndrome, what does this tell us?
there is a risk for both arterial thrombosis and miscarriage. Remember there isn't a risk for bleeding, only thrombosis.
** What is the diagnosis for an anti-phospholipid antibody syndrome?
demonstration of phospholipid dependence, positive tests on 2 occasions 12 weeks apart, and significant cardiolipin titer.
** Is thrombomodulin involved in protein C generation?
** Can excessive warfarin (Coumadin) therapy cause skin necrosis in patients with protein C deficiency?