Bleeding Disorders
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| 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
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| What lab tests do you order for bleeding disorders? | CDC, Platelet function test, Coagulation Test, Protein Assays
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| 4 Steps of Coagulation | Resting -> Adhesion -> Activation -> Aggregation
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| What molecules are involved in Adhesion? | vWF, GP Ib + GP 9, collagen
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| Explain Glanzman Thrombasthenia | Autosomal recessive disorder in which platelets lack the GP IIb/
IIIa receptor on the cell surface
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| 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)
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| 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
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| 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
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| 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
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| How do you treat ITP? | Acute: Usually goes away on its own
Chronic: 1) Steroids, IVIG
2) Splenectomy
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| 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*
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| What are some features of HIT? | Modest decline in platelet count, associated with arterial + venous thrombosis,
excessive thrombi formation, NO excessive bleeding
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| What are the types of diseases under Thrombotic Microangiopathy (TMA)? | TTP, Hemolytic Uremic Syndrome, DIC
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| What protein defect cause TTP? | ADAMTS-13 -> required for cleaving vWF causing excess aggregation of platelets.
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| Symptoms of TTP are: | Excess thrombi formation, fever, renal failure, transient neurologic deficits
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| 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
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| 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)
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| What is DIC? | Constant deplete of platelets that is caused by large amounts of intravascular microthrombi.
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| 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*
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| 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.
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| What causes DIC? | Sepsis
Trauma
Obstetric Complications
Pancreatitis
Malignancy (tumor)
Nephrotic Syndrome
Transfusion
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| 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.
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| 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
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| 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
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| Describe Hemophilia A | X-linked Recessive Disorder
Decreased production of Factor 8
Prolonged aPTT, but normal PT and *BT*
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| Describe Hemophilia B | X-linked Recessive Disorder
Decreased production of Factor 9
Prolonged aPTT, but normal PT and *BT*
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| 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.
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| 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
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| Why does liver disease/failure have possibility of resulting in coagulation dysfunction? | Almost all coagulation factors are created in the liver.
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| What does desmopressin do? | Increases the release of vWF by Weibel-Palade cells -> Good for vWD
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