Flashcards in Bleeding Disorders - Ch. 14 Deck (55):
Petechiae and purpura, normal PT and PTT, normal platelet count
Bleeding due to abnormalities in vessel walls
Major infection that can cause vasculitis, DIC, and abnormal bleeding
Meningococcemia (N. meningitidis)
Collagen defect --> microvascular bleeding
Vitamin C deficiency, bleeding
Scurvy --> collagen defect, microvascular bleeding
Cushing syndrome, bleeding
Excessive corticosteroid production --> protein wasting --> loss of perivascular support tissue --> microvascular bleeding
***Hereditary hemorrhagic telangiectasia (W-O-R syndrome)
AD, mutations cause TGF-beta signaling abnormalities, causing dilated tortuous blood vessels that bleed easily (nose, tongue, mouth, eyes, GI tract)
Systemic immune IgA nephropathy/vasculitis disorder -- immune complex deposition --> rash/palpable purpura, colicky abdominal pain, polyarthralgia, acute glomerulonephritis
4 general causes of thrombocytopenia
- Decreased production
- Decreased survival
Things that may selectively affect/inhibit megakaryotyes, causing thrombocytopenia
Cytotoxic drugs, thiazide drugs, alcohol, measles, HIV
Things that may decrease platelet production due to BM failure
B12 or folate deficiency, aplastic anemia, myelodysplastic syndrome, metastatic cancer, granulomatous disease, leukemia
A woman is pregnant, but the fetus has very few platelets. Cause?
Alloantibodies - the baby's platelets are destroyed by antibodies in the mother
A person with a mechanical heart valve has anemia and thrombocytopenia. Why?
Heart valve can cause damage to both RBCs and platelets
A patient receives a blood transfusion and develops thrombocytopenia. Why?
Platelets die over time in stored blood, so the patient's platelet concentration is diluted with transfusion
Large spleen + thrombocytopenia
Spleen can sequester platelets, causing thrombocytopenia
Autoantibody destruction of platelets, bleeding
Immune thrombocytopenic purpura
3 causes of secondary chronic ITP
- B cell neoplasms (CLL)
Antibodies against platelet glycoproteins 2b-3a or 1b-IX
What antibody type?
Immune thrombocytopenic purpura
Adult woman under 40, petechiae in skin and mouth, history of easy bruising, nose bleeds, and hemorrhaging after minor trauma. Menorrhagia and melena. Spleen appears normal, no LAD is noted.
Idiopathic chronic ITP
Adult woman under 40, petechiae in skin and mouth, history of easy bruising, nose bleeds, and hemorrhaging after minor trauma. Menorrhagia and melena. Splenomegaly and lymphadenopathy are notable.
Secondary chronic ITP - B-cell neoplasm
Thrombocytopenia, increased megakaryocytes in the marrow, large platelets in the blood, normal PT and PTT
Accelerated platelet destruction, causing increased thrombopoiesis
Child, recently had an upper respiratory viral illness, now presents with thrombocytopenia, petechiae, and purpura. PT and PTT are normal. Increased megakaryocytes in the marrow.
Drugs that cause thrombocytopenia via antibody recognition
Quinine, quinidine, vancomycin, heparin
A patient is being treated for an acute MI with IV heparin in the hospital. About a week after treatment, signs of bleeding begin. She barely survives a pulmonary embolism. Blood work shows antibodies against platelet factor 4
Heparin-induced thrombocytopenia (HIT) - Type 2
Receptor and co-receptor for HIV infection, found on megakaryocytes
An HIV+ patient develops thrombocytopenia of no other known cause. Why? (2)
- HIV infects megakaryocytes via CD4/CXCR4 and causes apoptosis
- HIV infects plasma cells and causes autoantibody formation against platelet 2b-3 complexes, leading to phagocytosis
Adult female, petechiae/purpura, fever, pallor, weakness, fatigue, transient neurologic deficits. Labs show thrombocytopenia, normal PT and PTT. PB smear shows schistocytes or helmet cells. BM biopsy shows increased megakaryocytes.
Thrombotic thrombocytopenic purpura (TTP)
Anti-ADAMTS13 autoantibodies (acquired form) or mutation (inherited)
Child started having bloody diarrhea, fever, and abdominal pain 3 days ago. Now presents to the ER w/ petechiae/purpura, oliguria, and hematuria. Labs show throbocytopenia, normal PT and PTT. PB shows schistocytes or helmet cells. BM biopsy shows increased megakaryocytes.
Hemolytic-uremic syndrome (HUS)
EHEC (or other) infection/toxin, causing endothelial damage, platelet activation, micro-thrombi, and inflammation
Defect in complement factor H, CD46, or factor I
Petechiae/purpura, mild thrombocytopenia, enlarged platelets in blood, GP1b-IX deficiency/mutation
Defective platelet adhesion (vWF receptor deficit)
Petechiae/purpura/bleeding, normal platelet amount, IIb-IIIa deficiency/mutation
Impaired platelet aggregation (cannot form bridges via fibrinogen)
Effect of uremia on platelets
Disrupts adhesion AND aggregation
Storage pool disorders
Defective release of thromboxane and ADP from activated platelets
Effect of aspirin on platelets
Inhibits production of TxA2 and PGs, which are needed for proper platelet function
Post-traumatic ecchymoses, prolonged bleeding after surgeries, bleeding into GI tract, GU tract, and weight-bearing joints
Coagulation factor deficiencies
Patient has obvious bleeding issue. Labs show normal platelet amount, prolonged PTT, decreased factor VIII level. Ristocetin activity is reduced.
Von Willebrand Disease
Why is factor VIII decreased in vWD types 1 and 3?
vWF stabilizes factor VIII, thus deficient vWF causes decreased factor VIII
What is Ristocetin?
Causes platelet aggregation via vWF binding to GP1b. Reduced if vWF is deficient.
Male, history of easy bruising and progressive joint pain, presents to the ER due to massive hemorrhage after falling from a tree. Normal platelet amount, prolonged PTT, decreased factor VIII level or activity.
Hemophilia A (factor VIII deficiency)
How to distinguish Hemophilia A from Hemophilia B?
ONLY from factor VIII and IX assays
A chronic alcoholic presents with excessive bleeding following minor trauma. Labs show normal platelet amount. PT and PTT are prolonged.
Liver disease --> deficient coagulation factors and epoxide reductase (vitamin K activation)
Triggers of DIC
- Amniotic fluid tTP (pregnancy complication)
- Septic endotoxins (E. coli, meningococcemia)
- Mucinous adenocarcinoma
- APL primary granules
- Ag-Ab complexes (SLE)
- Heat stroke or burns
Bilateral renal cortical necrosis
DIC thrombi w/in giant hemangiomas due to stasis and fragile BV trauma
DIC thrombi via meningococcemia causing massive adrenal hemorrhage and failure
Read more about DIC
Bleeding or thrombosis, thrombocytopenia, increased PT and PTT, decreased fibrinogen, D-dimer increase
Acute DIC is most often due to _____ and presents with _____
Obstetric complications; bleeding
Chronic DIC is most often due to _____ and presents with _____
Cancers (adenocarcinomas, APL); thrombosis
A patient is in the hospital and receives a transfusion of packed RBCs and/or platelets. Soon after, she develops a fever, chills, and dyspnea. She responds well to acetaminophen.
Febrile nonhemolytic reaction (transfusion complication)
Donor leukocytes secreting inflammatory mediators due to the foreign environment
A patient receives a blood transfusion and develops a severe anaphylactic reaction. Explain
IgA deficiency --> IgG antibodies develop against the IgA in the donor blood --> allergic reaction
A patient receives a blood transfusion and develops hives all over his body. Explain
Allergen in the donor blood --> IgE reaction in the patient
A patient receives a blood transfusion and develops fever, shaking chills, and flank pain. Hemoglobinuria. A direct Coombs test is positive. May progress to severe symptoms. Explain
IgM reaction to inappropriate ABO blood type, causing complement-mediated hemolysis and inflammation
Blood transfusion, low haptoglobin, high LDH, positive direct Coombs test, anti-Rh, anti-Kell, anti-Kid antibodies
Antibody type? To what?
Delayed hemolytic transfusion reaction
IgG - to foreign protein RBC antigens
Patient w/ COPD, blood transfusion, sudden SOB, respiratory failure, b/l pulmonary infiltrates, fever, hypotension
Due to what?
The donor was most likely what?
Transfusion-related acute lung injury (TRALI)
Lung neutrophil activation via antibodies from the transfused blood against MHC antigens
A mother of multiple children