HEMATOLOGY - platelet disorders + TRA Flashcards
EXAM 2 content
what are thrombocytes? what can they do?
thrombocytes = platelets
- irregularly shaped anuclear cytoplasmic fragments = not true cells
- needed for blood coagulation + control bleeding
- an injury to a blood vessel –> plates release adhesive proteins, coagulation & growth factors
- plates can assume different shapes + form extensions –> increase surface area & plug vascular openings to control bleeding – main component in primary hemostasis
what is the normal thrombocyte concentration in the blood?
150,000 - 400,000 platelets/mm3
- 1/3 platelets are pulled into spleen
what is thrombocytopenia? what kinds of risks can happen with lower level of plates?
thrombocytopenia = low plate count
- < 150,00 plates
- < 50,000 –> risk of hemorrhage w minor trauma
- 10,000 - 15,000 –> risk of spontaneous bleeding w/o trauma (mucous membranes like gums + nose bleeding, petechiae, ecchymosis, purpara)
- < 10,000 –> risk of severe spontaneous bleeding (fatal on GI, resp, or CNS)
what are the threshold for platelet transfusions?
- actively bleeding = transfused to keep plate counts of 50,000+ plates
- pt w/ thrombocytopenia needs surgery = transfused prior, increased to at least 50,000
- pts w/ below 10,000 –> transfused to prevent spontaneous bleeding
what is petechiae, ecchymosis, & purpura?
- petechiae = pinpoint round spots on skin bc of bleeding
- ecchymosis = bruising (escaped blood from tissues or ruptured blood vessels)
- purpura = patches of purple discoloration (from blood into skin + mucous membranes)
what are causes of thrombocytopenia, decreased platelet production?
- viruses: EBV, rubella, CMV, HIV
- drugs: thiazides, estrogens, quinine-containing drugs, chemo agents, ethanol
- nutritional deficiencies: vit b12 or folic acid
- chronic renal failure
- cancer
what are causes of thrombocytopenia, increased plate consumption? (these are what are are focusing on)
- heparin induced thrombocytopenia (HIT)
-immune thrombocytopenia purpura (ITP) - thrombotic thrombocytopenic purpura (TTP)
- disseminated intravascular coagulation (DIC)
what is heparin induced thrombocytopenia (a type of increased plate consumption)? cause? character? diagnosis? treatment?
a immune mediated reaction to heparin (unfraction or low molecular weight)
- results from: forming antiplatelet antibodies (plate activation + consumption)
- characterized by: precipitous drop in platelet count + venous/arterial thrombosis might occur bc of prothrombotic state
- diagnosis: blood test for anti-heparin platelet factor 4 antibodies
treatment:
- stop all forms of heparin, never give again –> check allergy list
- give direct thrombin inhibitors (ARGARTROBAN) – another anticoagulant
what is immune thrombocytopenia purpura (a type of increased plate consumption)? cause? manifestations? treatment?
- acute: antigen forms immune complexes with circulating antibody –> bind to receptors on plates –> destruction in spleen
- chronic: IgG autoantibodies against plate specific antigens – autoantibodies bind to platelet antigens –> antibody coated platelets removed from blood by macrophages in spleen
- clinical manifestations: petechiae, purpura, epistaxis & risk of severe bleeding
treatment:
- glucocorticoids: suppress immune responses & prevent sequestering + further destruction of spleen
- intravenous immune globulin (IVIG): increases plate count by interfering with phagocytosis of antibody coated platelets by macrophages (for chronic)
- splenectomy: plates are in or by the spleen
what are the drugs that can be a treatment for ITP (immune thrombocytopenia purpura)? what is the over class? which one is the exemplary? what do they do?
Thrombopoietin Receptor Agonists (TRAs) – stimulate production of platelets
- ROMIPLOSTIM (Nplate) – exemplary
- AVATROMBOPAG (Doptelet)
- ELTROMBOPAG (Promacta)
what is the mechanism of action of ROMIPLOSTIM?
ROMIPLOSTIM is a peptibody (combo of peptide & antibody) –> mimics thrombopoietin –> stimulates megakaryocytes – cells that become platelets
what are the therapeutic uses of ROMIPLOSTIM?
only AFTER traditional ITP treatments have failed
what are the adverse effects of ROMIPLOSTIM?
- arthralgia, dizziness, insomnia, pain in extremities, abdominal pain, myalgia, shoulder pain, dyspepsia, & paraesthesias
uncommon but serious:
- bone marrow fibrosis = bone forming cells replaced by fibrotic tissue
- hematologic malignancy – from stimulation of bone marrow cells
- thrombotic/thromboembolic complications – from excessive platelet production
what are the contraindications/precautions when taking ROMIPLOSTIM?
platelet count may drop to pretreatment levels when drug is discontinued
how do we administer ROMIPLOSTIM?
SQ
how do we know if ROMIPLOSTIM was effective? when will we see results, peak, & decline?
monitor platelet count
- usually rises 4-9 days after a single dose
- peaks at 12-16 days
- decreased by day 28
what is thrombotic thrombocytopenic purpura (TTP), a type of increased platelet consumption of thrombocytopenia?
where there are blood clots (thrombotic), low plate count (thrombocytopenic) & purple bruises (purpura)
what is TTP (thrombotic thrombocytopenic purpura) caused by? results? treatment?
caused by: deficiency of enzyme ADAMTS13 – processes von Willebrand factor
- inherited
- acquired: most common, having antibodies –> dysfunction of enzyme
results in: platelet aggregation/clumping + binding to endothelium of blood vessels –>
- vascular occlusion in organs
- jaundice
- purpura
- petechiae
- bleeding
- thrombocytopenia
- hemolytic anemia
- renal failure
- neuro changes
treatment:
- plasma exchange with fresh frozen plasma –> replenishes functional & removes abnormal ADAMTS13
- glucocorticoids: decreases antibody production & acquired forms of TTP
what is thrombocythemia? what is there a risk of?
thrombocythemia = thrombocytosis
- plates > 450,000 of blood
- essential (primary) thrombocythemia: a defect in bone marrow –> chronic, myeloproliferative neoplasm
- secondary (reactive) thrombocythemia: occurs during inflammatory conditions + excessive production of cytokines
- usually asymptomatic until count passes 1 million
- risk of: thrombosis (intravascular clot formation) & hemorrhage, even if asymptomatic
even though thrombocythemia has a risk of thrombosis (clots), how does it still increase of bleeding? (this can be related to DIC too since its part of increase plate consumption, thrombocytopenia)
still lots of bleeding bc of a lot of blood clot formation – consuming body’s plates –> not enough plates in bloodstream to control bleeding
what are the clinical manifestations of thrombocythemia?
microvasculature thrombosis –> ischemia in fingers, toes or cerebrovascular regions
- erythromelalgia: warm congested hands & fees w/ painful burn sensation – common in LE
- headache
- paraesthesia
what is the treatment for thrombocythemia?
goal: prevent thrombosis or hemorrhage – there is a risk of
- arterial & venous thrombosis
- bleeding
HYDROXYUREA: non alkylating myelosuppressive agent
- suppresses platelet production
low dose ASPIRIN: to alleviate erythromelalgia & transient neurologic manifestations
