Platelet and Bleeding disorders Flashcards

Question

# Heparin Induced thrombocytopenia “HIT” General

Answer 1

Acquired disorder Formation of IgG antibodies to **heparin-platelet 4 (PF4)** complexes Bind to and activates platelets 3% of unfractionated heparin patients 0.6% low-molecular-weight heparin (LMWH) patients HAD to have had a heparin product previously, this reaction is due to a secondary exposure

Answer 2

Prior heparin use Long duration of heparin use Surgery Pregnancy Trauma Inflammatory conditions

Answer 3

Typically asymptomatic Arterial or venous thrombosis Up to 30 days after diagnosis Bleeding is rare

Answer 4

**PF4 heparin antibody** testing Not many places do in house testing of this! Takes a few days to get results back

Answer 5

Consult hematology Discontinue all heparin products immediately! Hint: Unfractionated heparin (UFH) is commonly used to flush catheters Platelet transfusions may increase thrombogenic effect High risk for thrombotic events Should be treated with alternative anticoagulants Initiation of warfarin should be postponed until substantial platelet recovery

Answer 6

Argatroban weight-based infusion Direct thrombin inhibitor Fondaparinux (Arixtra) weight-based once daily injection Factor Xa inhibitor Prophylactic anticoagulation should continue until platelets >100,000/mcL Continue for 30 days Thrombosis treatment can be changed to warfarin after platelets >100,00/mcL DOAC (direct oral anticoagulant) use not standard yet

Answer 7

Avoid heparin exposure Document history of HIT in allergies If heparin products necessary, consult hematology Will need repeat PF4 antibody levels drawn

Answer 8

Uncontrolled activation of coagulation leading to depletion of coagulation factors and fibrinogen * Procoagulant substances trigger systemic activation of the coagulation system and platelets * Disseminated deposition of fibrin-platelet thrombi within the microvasculature Associated with Sepsis Burns Head trauma Pregnancy HELLP syndrome | typically already a very sick patient

Answer 9

Hallmark is: **Bleeding** Spontaneous bleeding IV lines Incisions Minor trauma Progressive **thrombocytopenia** **Thrombosis**: DVT Digital ischemia Gangrene

Answer 10

Progressive thrombocytopenia Fibrinogen DOWN Fibrin degradation products UP Platelets DOWN PT / INR UP PTT normal to UP D-dimer UP Peripheral smear Schistocytes

Answer 11

treat underlying condition HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) in pregnancy Delivery of fetus Removal of retained placenta Give Blood products and factor replacement

Answer 12

bleeding disorder, not platelet disorder X-linked recessive disorders Spontaneous cases possible **Hemophilia A** – Inherited deficiency of factor VIII **Hemophilia B** – Inherited deficiency of factor IX **Hemophilia C** – Inherited deficiency of factor XI

Answer 13

X-linked recessive hereditary disorder of **Factor VIII deficiency** 2nd most common congenital bleeding disorder Males almost exclusively affected Severe = < 1% Factor VIII Moderate = 1-5% Factor VIII Mild = > 5% Factor VIII Inherited deficiency of factor VIII Males almost exclusively affected 1:4000 births > ½ with severe disease Hemophilia A more severe bleeding than B (IX)

Answer 14

**Spontaneous hemorrhage** is hallmark of disease **Hemarthroses** 80% of hemorrhagic cases- bleeding into the joint capsule. Muscle bleeds GI bleeds Bleeding tendency—related to severity of deficiency **Older Hemophiliacs may be HIV + due to historically contaminated Factor VIII blood**

Answer 15

Hemarthrosis

Answer 16

Laboratory evaluation **Deficient Factor VIII Prolonged aPTT** Should correct if perform a mixing study If this does not correct, suggests acquired factor inhibitor

Answer 17

**Factor VIII concentrate infusion** Recombinant Factor VIII (no HIV risk) Calculation of Factor VIII dosage related to severity of bleeding. Failure to respond to Factor VIII suggest inhibitor production Desmopressin may be effective in mild cases (vWF release, carrier of Factor VIII) Prophylaxis Emicizumab (Hemlibra) infusion Monoclonal antibody that binds to both factor IXa and factor X, substituting for the role of factor VIII in hemostasis **AVOID Aspirin!**

Answer 18

**Deficiency Factor IX** 1:15,000 to 1:30,000 births > 1/3 with severe disease Presents clinically the same as Hemophilia A Treatment Factor IX concentrate replacement

Answer 19

Hemophilic arthropathy Infections from plasma products 1970s and 1980s HIV 50% Hepatitis C Most patients Family & pregnancy planning Cardiovascular disease

Answer 20

**Deficiency Factor XI** 1:1,000,000 births Ashkenazi and Iraqi Jews 1:450 Bleeding is variable Usually no spontaneous bleeding PTT prolonged in severe deficiency (Factor < 20%) Treatment Factor XI replacement

Answer 21

Most common inherited bleeding disorder

Answer 22

Symptoms: Type dependent, usually mild Epistaxis Easy bruising **Bleeding gums** Heavy menses Symptoms can range from mild or infrequent bleeding in type 1 VWD to severe, life-threatening bleeding in type 3 VWD * Mucocutaneous bleeding symptoms Easy bruising Prolonged or excessive bleeding from minor injuries Nosebleeds GI hemorrhage Heavy menstrual bleeding * Risk for bleeding following : Surgery or invasive procedures, Dental extractions Traumatic injury Childbirth

Answer 23

Platelet count: normal vWF levels: DOWN or dysfunctional Bleeding time: typically UP aPTT: often normal May be UP if deficiency of Factor VIII

Answer 24

**Prophylaxis** **DDAVP** (synthetic vasopressin) Promotes release of vWF from endothelial cells **Replacement therapy** vWF concentrate Factor VIII concentrate in some patients

Answer 25

Liver synthesizes and clears both procoagulants and inhibitors The hepatocyte is the production site of almost all numbered coagulation factors including fibrinogen (factor I), thrombin (factor II), and upstream factors V, VII, IX, X, and XI Exceptions Factor VIII, which is produced in endothelial cells Factor XIII A-subunit, which is produced in megakaryocytes Fibrinogen the last to fall **If concurrent Vitamin K deficiency (alcohol use), Affects ALL vitamin K dependent factors (X, IX, VII, and II “1972”)**

Answer 26

PT (INR) more prolonged than aPTT Distinguished from simple vitamin K deficiency by failure to respond to vitamin K replacement Structural manifestations of liver disease contribute to bleeding Portal hypertension Esophageal varices Gastritis Hemorrhoids

Answer 27

Nutritional depletion Alcoholics Long-term IV nutrition Antibiotic administration Interfere with bacteria synthesis and absorption Warfarin

Answer 28

Defined as transfusion of more than 1.5 times the patient’s blood volume in 24 h Acquired coagulopathy results from dilution of plasma and platelets and excess anticoagulant 10% of transfusion is anticoagulant **Prevention**: Administer 1-unit FFP and calcium chloride for every 4-6 units PRBC’s

Answer 29

MOA: Synthetic analogue of the antidiuretic hormone arginine vasopressin. In a dose dependent manner, desmopressin increases cyclic adenosine monophosphate (cAMP) in renal tubular cells which increases water permeability resulting in decreased urine volume and increased urine osmolality; increases plasma levels of von Willebrand factor, factor VIII, and t-PA contributing to a shortened activated partial thromboplastin time (aPTT) and bleeding time. Use: DI, Hyponatremia, Hemophilia A, ICH 2’ to antiplatelet agents, vWD Avoid in moderate to severe renal impairment Dosage forms: Intranasal, Inj/Infusion, Tablet Adverse effects: Hyponatremia, xerostomia, fluid retention

Answer 30

MOA: A humanized monoclonal modified immunoglobulin G4 (IgG4) antibody with a bispecific factor IXa- and factor X-directed antibody, bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis. Use: Hemophilia A prophylaxis to prevent or reduce the frequency of bleeding episodes with or without factor VIII inhibitors Initial: 3 mg/kg once weekly for 4 weeks Maintenance: 1.5 mg/kg once weekly or 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks Adverse effects: injection site reaction, headache, arthralgia Avoid in pregnancy (lack of studies)

Answer 31

Potentially curative treatment option for multiple malignant and benign diseases Also known as bone marrow transplant Patient receives healthy (unaffected) stem cells to replace their own

Answer 32

Autologous (patient’s own cells) Allogeneic cells from another person Sibling Parent or relative Unrelated Donor Source Umbilical cord Peripheral blood Bone marrow

Answer 33

1.Conditioning 2.Stem cell infusion 3. Neutropenic phase 4. Engraftment phase 5. Post-engraftment period

Answer 34

If donor cells see the host cells as foreign, they will attack the host Skin, gut, and liver most likely to be affected Acute < 100 days after the transplant Chronic > 100 days