Not Anemia (Polycythemia & Hemochromatosis)
What is the pathognomonic sign/symptom of Polycythemia Vera?
Aquagenic Pruritis
What tissues are especially dependent on platelets?
Skin, mucosal tissues.
Which of the following would indicate thrombocytopenia?
A)Nosebleeds
B)Menorrhagia
C)Significant gum bleeds with brushing
D)excessive bleeding after knee scrape.
All of them!
NOT hemarthroses or hematomas.
What tissues are especially dependent on clotting factors?
muscles, joints
Which clotting factor has the shortest half life?
What is the pathophysiology of hereditary hemochromatosis? What labs (CBC, Fe, Ferritin, TIBC) would you expect?
In HH, there is a genetic mutation resulting in deficiency or total loss of Hepcidin. Hepcidin normally "plugs the iron hole" in the GI tract and in macrophages, preventing iron absorption/secretion from macrophages. Less hepcidin = risk of iron overload.
CBC = high RBC (body tries to compensate for too much iron by making more RBCs)
Fe = High
Ferritin = High
TIBC = Low
What is the difference between kids and adults in the setting of Immune Thrombocytopenia (ITP)?
In adults, ITP is chronic, often idiopathic, and no rash is present.
Both can be secondary or induced by medications.
How do platelets get activated?
Platelets adherent to site of injury activate via conformational change of GPIIB/IIIA receptor -> increased binding to fibrinogen.
Once activated, they release their granules, which promotes platelet recruitment, aggregation and activation. Alpha granules have Platelet Factor IV, Dense granules have ADP, serotonin, and TXA2.
What pathways do PTT and PT test? What anticoagulants can alter PTT/PT/TT?
PTT = Intrinsic pathway (Adds surface factors to bypass need for VIIa). Sensitive to Heparin
PT = Extrinsic pathway (Adds III to blood). Sensitive to Warfarin
TT = Adds IIa (thrombin) and sees if you can make fibrin. Sensitive to Heparin.
What are 2 important functions of VWF?
In VWD, what is the most common sign/symptom?
VWF binds to GP1B receptors of platelets as well as collagen to aid in adhesion and aggregation of plts. It also binds to and stabilizes Factor VII, increasing half life 5x.
In VWD, most common presenting symptom is mucocutaneous bleeding. Coag panel may be prolonged or normal - VWD is the most commonly inherited bleeding disorder but most people aren't affected enough to present for medical care.
What is the most common cause of polycythemia vera? How is it treated?
Most cases are due to a genetic mutation in the gene coding for JAK2 Tyrosine Kinase.
Tx: Therapeutic phlebotomy, hydroxyurea (unsure of mechanism), myelosuppressive drugs.
What is the treatment of HUS? What other test can we do to potentially find the cause?
Mostly Supportive - Fluids, RBC transfusion, dialysis. Make sure to manage fluid overload from fluids/transfusion.
Stool studies to look for STEC shiga toxin. (Often will have bloody diarrhea preceding HUS)
Hemolytic Uremic Syndrome is defined as the simultaneous occurance of what 3 things?
Hearing Usher Sing = Many Asses Twerking
what is the most common VTE? What are some Acquired hypercoagulable states?
Most common VTE is a DVT of the lower extremity.
Acquired hypercoag states: Pregnancy, surgery, immobilization, malignancy, estrogen exposure (OCPs), obesity, history of thrombosis.
Explain the difference between an antithrombin deficiency and a prothrombin gene mutation.
Antithrombin is a natural anticoagulant, and prevents thrombin from converting fibrinogen to fibrin. Deficiency = higher chance of thrombosis. (Not enough brakes)
Prothrombin gene mutation increases production of prothrombin, which is the precursor to thrombin. More prothrombin --> more thrombin --> more fibrin. (too much gas)
A patient comes in with hepatomegaly and a gray-bronze hue to their skin. What disease is this, and what is the treatment options for the patient?
Hemochromatosis
Tx: Refer to hematology for liver biopsy/genetic testing. Therapeutic phlebotomy to get rid of some iron can help.
PT ED: Avoid alcohol (expression of disease modified by alcohol intake & diet)
What 2 platelet receptors are important for adhesion? Which is important in activation?
Adhesion: GPIA/IIA receptor binds to collagen in subendothelium, GP1B receptor binds to VWF.
Activation: GPIIA/IIIB undergoes conformational change that increases binding to fibrinogen.
in Heparin-Induced Thrombocytopenia, IgG autoantibodies attack what molecule(s)? How does the patient become thrombocytopenic?
Which diseases would lead to a prolonged PT?
A) Hemophilia A
B) Vitamin K deficiency
C) Disseminated Intravascular Coagulation
D) Prothrombin gene Mutation
B and C
Hemophilia A would have a prolonged PTT (Factor VIII)
Prothrombin gene mutation would have a shorter PT (higher clot risk)
What is the most common thrombophilia? How does it result in thrombosis?
Factor V Leiden! (autosomal dominant)
mutation in gene in F5 gene abolishes cleaving site of protein C (which normally breaks down Factor V). less activation of protein C = less breakdown of Factor V = clots.
Similar process as a Protein C or S deficiency.
A patient comes in with a headache, and erythematous complexion. Vitals show a BP of 146/95. Upon exam, you notice significant hepatosplenomegaly. Labs return, and the CBC shows high WBC/RBC/Plt counts. What is a serious (non-cancer) complication you should be worried about?
Venous and/or arterial thrombosis (more RBCs/platelets -> higher risk of clot)
Explain how Thrombotic thrombocytopenic purpura (TTP) leads to a microangiopathic hemolysis?
TTP results from a deficiency of ADAMTS13, a protease that breaks down Von Willebrand Factor. Low ADAMTS13 = high VWF = more thrombi. Results in a microangiopathic hemolysis as RBCs are shredded as they are pushed through fibrin clots. Thrombocytopenia ensues as plts are all being consumed.
Smear Key Finding: Schistocytes (shredded RBCs s/p hemolysis)
A patient presents with a headache, intermittent vision changes, and complaints of a syncopal episode yesterday. Upon exam, you note a purple, reticular "lacy" rash and splenomegaly. What particular disease should be on your differential?
Thrombocytosis. High risk for thrombosis. Treatment depends on original cause (most are secondary, but if primary, probably malignancy), but refer to heme/onc.
Explain the pathophysiology of Anti-phospholipid antibody syndrome, and how it relates to Syphilis. What is the treatment?
Anti-phospholipid antibody syndrome: autoantibodies attack phospholipid-binding proteins involved in coagulation cascade (most commonly anti-cardiolipin and anti-beta2-glycoprotein). Anti-cardiolipin Antibodies also associated with syphilis infection, so these people will have a positive VDRL (syphilis screening test). No pathognomonic findings, but may show signs of ischemia or infarct (eg. digital gangrene).
Treatment involves anticoagulation if they have a VTE, but not prophylactically.
For Hemophilia...
-What factors affected for A & B subtypes?
-Most common areas of bleeding?
-Any abnormal lab values?
-Treatments?
1) A: Factor 8. B: Factor 9
2) Hemarthroses and hematomas
3) prolonged PTT
4) DDAVP (synthetic analog of ADH that promotes release of VIII and VWF). Also plasma transfusion for clotting factor replacement.