Bleeding Disorders Flashcards
Hemophilia A and B
Both are X-linked inheritance & can’t be distinguished clinically
Hemophilia A: VIII deficiency
Hemophilia B: IX deficiency
Cerebral & soft tissue hemorrhage, hematuria, GI bleeding, surgical bleeding, epistaxis (nosebleeds), hemarthrosis (bleeding into joint spaces), hematoma
Mild: >5% factor activity, treat on demand
Moderate: 1-5% of factor activity; variable penetrance
Severe: <1% of factor activity; require prophylactic treatment
Treat with prophylactic factor replacement, given IV
VIII: 3x weekly
IX: 2x weekly
On demand factor replacement dosing is variable
Von Willebrand Disease: what it is, symptoms, 3 subtypes
Autosomal dominant, most common inherited hemorrhagic disorder
Normal PTT and PT
Menorrhagia, easy bruising, dental/surgical bleeding
Subtypes: 1 = very mild and very common!! might not know they have it
2 = functional impairment, very rare
3= absent synthesis, very very rare
vWF: binds collagen, protect factor VIII, binds platelets
How do you diagnose vWD?
Low factor VIII (bc vWF binds and protects it)
Low vWF antigen
Low vWF:RCo activity: tests how much vWF you have because you should get normal aggregation when you expose it to ristocetin (an antibiotic, not used clinically but used to diagnose vWD)
** the values for the above are low in subtype 1 and VERY low in subtype 3
vWF Ag:RCo ratio: >50% in 1, <50% in 2, very very low in 3
vWF multimers: Normal in 1, 2 depends on subtype, very abnormal in 3
What is the treatment for vWD?
Depends on severity: least to most severe:
Less severe: no treatment, contraceptives for women with menorrhagia
Aminocaproic acid: blocks plasmin synthesis, which prevents breaking up of clots that have formed
Desmopressin (ddAVP): presses on endithelium to get surge of vWF and VIII
vWF concentrates
Most severe: Cryoprecipitate (process blood so it’s rich in VIII and vWF; last resort bc it comes from blood products and might have potential pathogens)
Hemophilia C
Factor XI Deficiency
Autosomal recessive
aPTT often but not always prolonged; you’re oblicated to check for XI deficiency if you see a mild increase in PTT
Sometimes discovered during surgery
Treat with fresh frozen plasma
Ashkenazi
Vitamin K Deficiency
Can be due to antibiotics (because you get it from your gut flora) and malnutrition
“K is for Koagulation”
Oxidized Vitamin K is the active one
When you deplete Vitamin K, Factor VII will take over and is responsible for the long PT but normal PTT
ITP: what is it, how do you diagnose it
Immune thrombocytopenic purpura: this is the bleeding analog of the Coombs positive, autoimmune hemolytic anemia
Petichiae and purpura: skin manifestations happen when you have platelet related bleeding!
Autoimmune reaction against platelets: the platelets or ITP are giant platelets
B cells get disregulated & start making antibodies against platelets
These platelets pass thru the spleen & get recognized by antibody receptor macrophages there –> get eaten up by macrophage in one bite
Diagnosis of exclusion, but may be found in other conditions: MUST TEST FOR Hep C and HIV
- also seen in lupus, sarcoidosis, leukemia, lymphoma, solid tumors, etc.
Normal white count, normal Hb count, low platelet count
How do you treat ITP?
Steroids: prednisone, dexamethasone
IV Ig’s
IV anti-D (WinRho) - the med given to preg women that are Rh+ with an Rh- baby; antibodies to pt’s own RBC so redirects macrophages so they attack the RBC instead of plts
Splenectomy
Rituximab (anti-B cell antibody)
Thrombopoietin mimetics: to drive plt production
Romiplostim, eltrombopag
Uremic platelet dysfunction
Patients in renal failure are more likely to bleed because your kidneys filter some type of chemical that’s toxic to the platelets; in kidney failure, can’t do this
Plt dysfunction, endothelial dysfunction, treat with dialysism, desmopression acutely
Poisoned platelets
Aspirin, NSAIDS, clopidogrel, prasugrel, alcohol
Medication induced thrombocytopenia
Antibody formation (penicillins)
Bone marrow suppression (chemo, anti-rejection Rx, alcohol)
Other causes of thrombocytopenia
Sepsis
Infections & cancers that invade bone marrow
Splenomegaly
Leukemias, MDS
Pelvic radiation: for cervical/prostate cancers
Aplastic anemia: deficiency of all 3 blood cells
Rare inherited plt disorders
Bernard-Soulier syndrome: absence of gp1B vWF receptor
Glanzmann Thrombasthenia: absence of GpIIB/IIIA receptor (fibrinogen recetor)
May-Heggalin anomaly: macrothrombocytopenia secondary to non muscle myosin heavy chain mutation
Grey Platelet syndrome: plt granule packaging defect
Hermansky-Pudlak Syndrome: platelet granule packaging defect, strongly associated with albinism
DIC: what it is and how you get it
“Consumptive coagulopathy”
Coag cascade is too active due to infeciton, hypertransfusion, disseminated carcinoma, leukemia, envenonations, surgery, bleeding = you use too much of your clotting proteins
Leaves you susceptible to bleeding elsewhere in the body
Presents as bleeding from access sites/recent surgical sites, purpura & gangrene
DIC diagnosis?
Increased PT and PTT bc all your clotting factors are depleted
Decreased fibrinogen bc it’s all getting used up
Increased D-dimer bc you’re coagulating
Decreased platelets bc they’re getting used up
Possible to get schistocytes bc you get microthrombi in circulation as the macrophages bite out of the RBCs
