Pharm 562 - Blood products, Thrombocytopenia, Clotting disorders
Terms in this set (20)
Why is thrombocytopenia a problem, and what is it? What are some S &S?
Bleeding complications. spontaneous bleed.
It's when platelets too low.
<100,000 (normal is 150,000-450000/microL
S&S: bruising, petechiae, purpura, epistaxis, bleeding from mucous membranes, menorrhagia.
What platelet levels are reduced? What level indicates transfusion? Circulating time?
TRANSFUSION TRIGGER: <10,000/microL = frequent spontaneous bleed.
10-50K - rare spontaneous bleed
50-100K - increased bleeding risk.
Circulating time is 5-10d so expect platelet nadir.
What are the major causes of thrombocytopenia? What disease states are associated with each?
DECREASED PRODUCTION (by bone marrow) - Drugs, radiation therapy, infections, diseases, B12 or folate deficiency, congenital.
INCREASED SEQUESTRATION - splenomegaly (spleen won't release)
INCREASED DESTRUCTION - TTP, fever, blood loss, drug (immune), combo destruction and decreased production (ITP)
Drug-induced thrombocytopenia: Which are the frequent culprits (classes) and their mechanisms? How should you manage? When to expect improvement?
Immune Ab/destruction: heparin, quinine, gold salts, phenothiazines, sulfonamides, antibiotics
1. remove offending drug (look at OTC's, tonic water)
2. Platelet transfusions for overt hemorrhage
3. Counts begin to rise in 1-2d, normal at 1-2w
4. Don't re-challenge drug!
Which two medications are also available to combat thrombocytopenia? Why not used?
1. Oprelvekin (Neumega) - IL-11 analogue.
MOA: Makes early cells, and they mature faster so less need for transfusions, less time to recovery.
AE's - TOXIC!! fluid retension (pulmonary edema), cardiotoxic.
2. Thrombopoietin (TPO) - can cause neutralizing antibodies! Approved ONLY for ITP.
What are the causes of ITP? Consequences? Major treatment modalities/step treatment?
1. ITP = Idiopathic (immune) thrombocytopenia purpera. ONLY platelets low. Dx of exclusion. Ab's against platelet surface glycoproteins.
a) suppress the immune systm - GC high dose like 40mg dexamethasone + rituximab 375mg/m2. (combo showed 20% better response for longer time.) Minor AE's.
b) Prednisolone; IVIG - IV immunoglobulin (rxns); Rho D immune globulin for Rh positive only; splenectomy (for refractory ITP. infection risk for rest of life)
c) Chronic refractory >3mos, failed second-line options, platelets <50K: TPO-mimetic.
What are the TPO-mimetics used in ITP? AE's, DI's, monitoring?
-Romiplostim (Nplate) REMs: NPlate NEXUS
-Eltrombopag (Promacta) REMs: Promacta CaresTM
AE: neutralizing Ab's! fibrosis, contusion, abd pain, bleeding if <20K platelets, arthralgias, hepatotoxicity (eltrombopag).
MONITORING: weekly CBC during titration, until stable for 4w, then monthly.
DI's with Promacta: cations - decreased abs; statins - increased levels because OATP1B1 inhibitor; CYP1A1 inhibitors like CIPRO, SSRI's, may slow metabolism (toxic levels of TPO)
What are the causes of TTP? What are the 5 sx? Consequences? Major treatment modalities/step treatment?
TTP = thrombotic thrombocytopenia purpura
1)Drugs that cause: Quinine, mitomycin C, cyclosporine, tacrolimus (esp with sirolimus)
2) e.coli 0157
3) deficiency or Ab's against ADAMTS13
**All 5 sx must be present: thrombocytopenia, microangiopathic hemolytic anemia, renal failure, neuro sx, fever.
TREATMENT: Remove agent, NO platelet transfusion!!!, daily plasma exchange with FFP or cryosupernatant plasma (daily plasma exchange)
Chemotherapy-induced thrombocytopenia: Agents, mechanism, treatment?
Direct toxicity - less megakaryocytes in bone marrow
DRUGS: carboplatin, gemcitabine, taxanes, alkylating agents, MTX, cytarabine
TX: Delay chemo or lower dose. If platelets <100K, hold next cycle until back up.
Transfusion if <10,000/microL
What are the three most common clotting disorders? Etiology, sequelae, treatment options for each?
1. Hemophilia A - 85%. Factor VIII deficient. X-linked recessive.
TX: a)Mild (5-50%)- Desmopressin (DDAVP) prior to minor surgery. Factor 8 for major surgery. causes release of Factor VIII and von Willengrand from storage.
b) Moderate (1-4% of normal) Severe (<1%) - Factor VIII replacement: FFP, cryoprecipitate, FVIII concentrates or recombinant. DDAVP won't work!
2. Hemophelia B - Factor IX def. x-linked.
TX: FFP, Factor IX concentrates or recombinant.
Von Willebrand disease - DDADP before dental procedures. Type 1 heterozygous more common, less severe. Type 2 = qualitiative defect. Type 3 = no vWF.
TX: FFP, cryoprecipitate, DDAVP (type 1 only), or Factor VIII concentrates that contain vWF (avoid ultra-high purity products). Use Humate-P, Koa-te-DVI, Alphanate
What is the indication, dose, AE's of desmopressin?
Minor bleeding in Hemophilia A
Dose: 0.3mcg/kg IV over 15-30 mins pre-procedures. 2x increase in Factor VIII is response. Repeat daily x2-3d until tachyphylaxis
AE's: facial flushing, water retension.
What is a FVIII recombinant product?
Intermediate or severe Hemophilia A.
Lower risk of BBP transmission.
Dose: 0.5IU/kg x % desired increase of F VIII x wt(kg)
In F VIII inhibitor disorder, give higher dose for low titer of neutralizing antibodies.
High titer inhibitor - use activated prothrombin complex concentrate or recombinant Factor VIIa
What are the Factor IX recombinant products? Dose?
Alphanine, Mononine, Benefix.
Dose: 1.2 IU/kg x % desired increase x kg
Same for peds except 1.4 IU/kg
Factor 9 inhibitor disorder: neutralizing Ab's
Low inh titer: give higher dose of Factor 9
High inh titer: bypass F 9 with activated prothrombin complex concentrate or recombinant factor VIIa.
What are the blood products, and what are they used for? What are the expected results from transfusion?
1. PRBCs - expect 1 unit to result in 1g/dL Hb, Hct by 3%
2. Platelets 1 unit for 5000-1000 mcg/L
3. Whole blood (not used often)
4. FFP - fresh frozen plasma (incl. clotting factors. Consider in warfarin overdose.) 1 unit (200-250mL) = 2% increase in coag factors
5. Cryoprecipitate - with Factor VIII, von Willebrands factor, fibrinogen. 10-15mL gives 80 units Factor VIII. Used for congenital d/o.
6. Granulocytes - reactions due to WBCs from someone else.
What are the major risks from transfusions?
1. Transfusion reactions ( major! Look for fever spike soon after tranfusion)
3. blood-borne pathogen transmission
4. Volume overload (watch CHF pt)
5. Graft vs host disease (GVHD) in immunosuppressed pts
6. Iron overload with PRBC's. HIGH levels - myelodisplastic syndrome patients.
What are S&S of transfusion reactions? RF's? What is used for pre-medication?
Sx/signs = fever, hives, capillary leak, hypotension, SOB
RF's: higher number of transfusions (Ab formation)
PREMED: Diphenhydramine, APAP, steroids
What are three measures taken to reduce the risk of transfusion reactions in higher-risk patients?
1. Leukocyte reduction filters (PRBCs, Platelets). Less risk of febrile rxn, transmit CMV, refractoriness.
2. Irradiation (PRBCs, Platelets) - less GVHD
3. ABO-compatible platelets - (Platelets) less refractoriness.
Which two factors primarily influence platelet formation from stem cells?
IL-11 and TPO
Refresher on heparin-induced thrombocytopenia: Which to worry about? Its profile?
HIT II - more rare, but dangerous. Platelet aggregation, 5-14d onset (repeat 1-3d), <100K platelets (usually 50% drop). NOT REVERSIBLE! Thrombosis, amputation, death.
How is HIT II treated?
D/C all heparin (incl LMWH)
Begin alternative: direct thrombin inh (bivalrudin, argatroban), avoid warfarin alone.
NEVER USE AGAIN.
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