Approach To Bleeding Flashcards
Unique characteristic of megakaryocytes.
Ability to continue DNA synthesis without undergoing mitosis.
What signals pluripotent stem cells to form into platelets?
Some signal causes growth factors, mainly thrombopoietin from the kidney and liver to be released into blood. Thrombopoietin goes to the bone marrow and signals the CD34+ stem cells to differentiate into megakaryocytes.
Function of GPIb-IX-V
Binds platelets to vWF
Function of GPIa-IIa and GPVI
Bind platelets to collagen
Function of GPIIb/IIIa
Binds fibrin. Allows platelets to bind each other.
Name the 4 things in platelet alpha granules.
- vWF
- Factor V
- Plasminogen Activator Inhibitor-1 (PAI-1)
- Fibrinogen
Name the 3 things found in platelet dense granules.
- ADP/ATP
- Serotonin
- Calcium
Location of Alpha-2 Antiplasmin
Bound to Factor XIIIa
Factor XIII crosslinks fibrin monomers to make a soft clot into a hard clot
What is a mixing study?
Test done after both a prolonged PT and prolonged PTT. Patient’s blood is mixed with normal blood. If the either one corrects, the defect was a Factor deficiency. If neither correct, the defect is a Factor inhibitor.
What is the minimum platelet count that is well-tolerated by the population?
10,000/uL
What is the minimum platelet count that surgeons want to see before an operation?
50,000/uL
Most common cause of Thrombocytopenia due to production defects.
Bone marrow is infiltrated by malignant cells. Interferes with normal stem cells to produce blood cells including megakaryocytes.
Most common cause of Thrombocytopenia due to abnormal sequestration.
Hypersplenism: splenomegaly resulting from accumulation of blood products in the spleen.
Pathology of DIC.
Disseminated Intravascular Coagulation
-some trigger simultaneously activates both thrombin and plasmin eliminating clotting factors rapidly. The result is both bleeding and microvascular thrombosis.
In patients with DIC, what lab values are expected?
- Platelets
- PT
- PTT
- Fibrinogen
- D-Dimers
- Decreased (thrombocytopenia)
- Increased
- Increased
- Decreased
- (+) Test
What is the D-dimer test?
D-dimers are a byproduct of plasmin degredation of fibrin monomer units in a clot.
Tx for DIC.
- reverse underlying cause (infection, drugs etc)
- Replace platelets and coagulation factors
Pathogenesis of TTP and HUS.
- Activation of platelets causing microthrombi in small capillaries.
- Ischemia to organs occurs, most commonly kidneys and brain (TTP)
- Micro thrombi also cause lysis of RBCs as they rub across the thrombi at high velocity.
Cause of platelet activation in Hemolytic Uremic Syndrome (HUS).
Damage to endothelial cells by the Shiga Toxin.
Cause of platelet activation in TTP.
Large multimers of vWF accumulate due to lack of ADAMTS13 which normally cleaves them.
What are the symptoms of HUS and TTP
Both: Thrombocytopenia, Renal Failure, hemolytic anemia
TTP only: fever, neurologic symptoms
What labs are expected with HUS and TTP
- Platelets
- Bilirubin
- LDH
- Haptoglobin
- PT
- PTT
- Blood Smear
- Low
- increased
- Increased
- decreased
- normal
- normal
- shcistocytes
Presentation of pre-Eclampsia and HELLP syndrome.
pre-Eclampsia: HTN, proteinuria, edema
HELLP: Hemolysis, Elevated Liver Enzymes, Low Platelets
Etiology of both unclear
Tx of pre-Eclampsia and HELLP
Deliver baby
Mechanism of Drug-Induced Immune Thrombocytopenia.
Some medication changes the surface epitope on platelets. This causes the body to recognize the platelets as “foreign” and Abs are produced to remove them.
Mechanism of HIT.
Heparin Induced Thrombocytopenia
- heparin normally binds platelet factor 4 (PF4 or Antithrombin III) preventing its activation.
- the body recognizes the heparin-PF4 complex and activates platelets as an immune reaction causing clotting.
Tx of HIT
Stop Heparin
Use direct thrombin inhibitors
Pathogenesis of ITP.
Immune thrombocytopenic purpura
-autoAbs against platelets are produced.
What lab values result from ITP
Only low blood count is platelets
Marrow biopsy shows megakaryocyte hyperplasia
(diagnosis of exclusion when all other causes are ruled out for thrombocytopenia. Skin has purpura)
Tx for ITP.
Prednisone IVIG (Intravenous IgG that recognizes the autoantibodies, binds them, and inactivates them)
Defect in Glanzmann Thrombocytopenia.
Autosomal Recessive
GPIIb/IIIa defect
Defect in Bernard Soulier Syndrome
Abnormal GPIb-IX-V protein
-giant platelets because of the GP role in megakaryocyte development
Why don’t you give NSAIDs with ASA?
NSAIDs can interfere with the anti-platelet effect of ASA, potentially rendering aspirin less effective when used for cardioprotection and stroke prevention
