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Bleeding Disorders

What are some physical examination findings that you see on patients with bleeding disorder? Epistaxis, Petechiae, purpura, ecchymoses, edema, oral mucosal bleeding, Telangiectasia (spider veins), menorrhagia
What lab tests do you order for bleeding disorders? CDC, Platelet function test, Coagulation Test, Protein Assays
4 Steps of Coagulation Resting -> Adhesion -> Activation -> Aggregation
What molecules are involved in Adhesion? vWF, GP Ib + GP 9, collagen
Explain Glanzman Thrombasthenia Autosomal recessive disorder in which platelets lack the GP IIb/ IIIa receptor on the cell surface
What is GP IIb/IIIa for? They are proteins expressed on the platelet membrane that is important in platelet aggregation. (GP IIa/IIIb from 2 different platelets attach to 2 opposite ends of fibrinogen)
Explain Bernard-Soulier Disease Disease that occurs when platelets lack GP Ib on their surface. These cells can't bind to vWF -> resulting in inability of adhesion
What is ITP? What are the two types? ITP is a disease where autoantibodies are formed against platelets cause thrombocytopenia. The two types are Acute and Chronic
Explain Acute vs. Chronic ITP. Which age group is more likely to get Acute ITP? Chronic ITP? Acute ITP has sudden onset of symptoms. Chronic ITP has gradual onset of symptoms from *IgG formed against GP IIa/IIIb*. Children (2-10) get mostly acute Teenagers and Adults get mostly chronic
How do you treat ITP? Acute: Usually goes away on its own Chronic: 1) Steroids, IVIG 2) Splenectomy
How does Heparin-Induced Thrombocytopenia occur? When Heparin is induced, heparin may bind to platelet factor 4 -> This creates heptan, which can be recognized as foreign antigen -> Body makes antibodies for it -> this *activates platelets*
What are some features of HIT? Modest decline in platelet count, associated with arterial + venous thrombosis, excessive thrombi formation, NO excessive bleeding
What are the types of diseases under Thrombotic Microangiopathy (TMA)? TTP, Hemolytic Uremic Syndrome, DIC
What protein defect cause TTP? ADAMTS-13 -> required for cleaving vWF causing excess aggregation of platelets.
Symptoms of TTP are: Excess thrombi formation, fever, renal failure, transient neurologic deficits
What is the name of the disease that is part of TMA and is caused by toxins from E. Coli? What is the toxin? Hemolytic Uremic Syndrome. Toxin is called Shiga-like Toxins
Compare TTP with HUS. They share symptoms of fever, anemia, thrombocytopenia (FAT) HUS patients present with more renal failure. (N) TTP patients present with more neurologic deficiency. (R)
What is DIC? Constant deplete of platelets that is caused by large amounts of intravascular microthrombi.
What do you see in patients with DIC? Depletion of platelets and clotting factors, widespread clot throughout body, excess bleeding (potentially hemorrhagic shock), *INCREASED level of D-Dimers*
Why do you see elevated D-Dimer in DIC? The body is constantly forming plasmins to degrade the clot -> Giving very high levels of lysed products which are D-Dimers.
What causes DIC? Sepsis Trauma Obstetric Complications Pancreatitis Malignancy (tumor) Nephrotic Syndrome Transfusion
Describe von Willibrand's Disease Common autosomal dominant disorder that is caused from decrease or abnormal vWF Patient will have increased bleeding time (BT) and PTT. Abnormal ristocetin cofactor assay.
How are the two types of vWD different? vWD Type 1 - vWF Ro: Ag ratio is >.7 -> Problem with vWF production vWD Type 2 - vWF Ro: Ag ratio is <.7 -> Problem with vWF function vWF Ag = immunoassay vWF Ro = function assay
What are the different types of Coagulation Tests? Describe each one. PT - extrinsic factors = 8, 9, 10, 11, 12 aPTT - intrinsic factors - 7, 10 TT - fibrinogen - looks to see if fibrinogen can be turned into fibrin
Describe Hemophilia A X-linked Recessive Disorder Decreased production of Factor 8 Prolonged aPTT, but normal PT and *BT*
Describe Hemophilia B X-linked Recessive Disorder Decreased production of Factor 9 Prolonged aPTT, but normal PT and *BT*
Coagulation Factor Inhibitor mostly targets which factor? CFI usually makes antibodies for Factor 8. The presentation is same as Hemophilia A, except that mixing with normal blood does not resolve the increase in PTT.
Which Vitamin deficiency leads to clotting problems? Why? Vitamin K -> factors II, VII, IX, X and protein C and protein S are all dependent on Vitamin K
Why does liver disease/failure have possibility of resulting in coagulation dysfunction? Almost all coagulation factors are created in the liver.
What does desmopressin do? Increases the release of vWF by Weibel-Palade cells -> Good for vWD
Created by: soobyung92
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