NOTES
NOTES
THROMBOCYTOPENIA
GENERALLY, WHAT IS IT?
PATHOLOGY & CAUSES DIAGNOSIS
▪ Acquired/inherited disorders: impaired LAB RESULTS
platelet function, decreased platelet count, ▪ Complete blood count (CBC)
sequelae ▪ Peripheral blood smear analysis
▪ Accelerated destruction/consumption → ▪ Platelet function tests
decreased platelets
TREATMENT
SIGNS & SYMPTOMS OTHER INTERVENTIONS
▪ Mitigate complications of deranged platelet
▪ Mucocutaneous bleeding (e.g. epistaxis, function
gingival bleeding, petechiae, purpura)
HEPARIN-INDUCED
THROMBOCYTOPENIA (HIT)
osms.it/heparin-induced-thrombocytopenia
▪ Increased consumption of platelets for
PATHOLOGY & CAUSES clotting + removal of antibody-heparin-
PF4 complexes by macrophages
▪ Acquired platelet disorder of reticuloendothelial system →
▫ Accelerated thrombosis in arteries, veins thrombocytopenia
→ consumptive thrombocytopenia. ▫ Thrombocytopenia usually not sufficient
▫ Occurs in individuals exposed to to cause significant bleeding
unfractionated heparin/low molecular ▪ Classified by severity, timing, degree
weight heparin (LMWH) of drop in platelet count drop, antibody
▫ AKA heparin-induced thrombocytopenia mediation
thrombosis (HITT)
▪ Exposure to heparin/LMWH → IgG RISK FACTORS
autoantibodies formed against heparin
▪ 5% individuals exposed to unfractionated/
→ platelet factor 4 (PF4) binds to heparin
LMWH
→ antibody-heparin-PF4 complex →
increased platelet activation → thrombosis ▫ Unfractionated > LMWH
formation in arteries, veins
OSMOSIS.ORG 455
▪ Dose
▫ Prophylactic dose > therapeutic doses >
DIAGNOSIS
intermittent heparin flushes
LAB RESULTS
▪ More common in individuals who are
biologically female HIT antibody testing
▪ HIT immunoassay
▫ ELISA for anti-PF4 antibodies
▫ PF4 antibodies in individual’s serum
▫ Colorimetric change: optical density
(OD), HIT antibody concentration
▫ Higher OD = higher antibody titer = HIT
▪ Functional assay
▫ Serotonin release assay (SRA)
▫ Serotonin release from platelets, ability
of HIT antibodies from individual’s
serum to activate test platelets
▫ Release of serotonin + therapeutic
heparin concentration
▪ Heparin-induced platelet aggregation
(HIPA) assay
▫ Platelet aggregation with no heparin,
low/high heparin concentration
▫ Minimal platelet aggregation with no
heparin, high heparin concentrations;
strong aggregation with low heparin
concentrations
COMPLICATIONS
▪ Venous thromboembolism (VTE) OTHER DIAGNOSTICS
▪ Occlusion of large lower limb arteries by ▪ History of exposure to unfractionated
platelet rich “white clots” → limb ischemia, heparin
necrosis, gangrene, loss of limbs ▪ New venous/arterial thrombosis
▪ Skin necrosis
▪ Organ infarction
▫ Kidney, myocardial infarction; MNEMONIC: 4Ts
cerebrovascular insult Diagnosis of
▪ Adrenal hemorrhage Thrombocytopenia
▫ Adrenal vein thrombosis Thrombocytopenia: CBC, fall in
▪ Heparin-induced anaphylactoid reactions platelet count
Timing: fall in platelet count,
5–10 days after heparin
SIGNS & SYMPTOMS initiation
Thrombosis: venous/arterial
▪ Skin necrosis at injection site thrombosis, sequelae
▪ Acute systemic reaction after IV heparin OTher: no other explanations
bolus
▫ Fever with chills, tachycardia,
hypertension, dyspnea
▪ Limb ischemia, organ infarction
456 OSMOSIS.ORG
Chapter 59 Thrombocytopenia
▫ Transition to warfarin/other outpatient
TREATMENT anticoagulant after stabilization
MEDICATIONS
▪ Immediate discontinuation of heparin SURGERY
▪ Administration of non-heparin Thromboembolectomy
anticoagulant (e.g. fondaparinux, ▪ If severe limb ischemia, high risk for
argatroban) amputation
IDIOPATHIC THROMBOCYTOPENIC
PURPURA (ITP)
osms.it/idiopathic-thrombocytopenic-purpura
malignancy, chronic lymphocytic leukemia
PATHOLOGY & CAUSES ▫ Alter immune homeostasis
▫ Alterations in T cell-mediated
▪ Acquired thrombocytopenia; accelerated
cytotoxicity/suppression of
immune platelet destruction → bleeding
megakaryocyte production, maturation
▪ AKA, immune thrombocytopenic purpura,
autoimmune thrombocytopenic purpura Drug-induced immune thrombocytopenia
▪ B cells produce IgG autoantibodies against (DITP)
platelet glycoproteins (e.g. IIb/IIIa, Ib/ ▪ Triggered by drug-dependent platelet
IX complexes) → platelets coated with antibodies
antibodies recognized as “non-self” by ▪ Quinidine, phenytoin, valproic acid,
splenic macrophages → platelet destruction rifampin, trimethoprim-sulfamethoxazole,
▫ Contributing factors: impaired platelet sulfonamides
production, cell-mediated platelet ▪ Reaction due to drug/metabolites
destruction
Severe ITP
TYPES ▪ Platelet counts < 10,000–20,000/microL;
significant bleeding requires treatment
▪ Classifed by cause, duration, severity
Refractory ITP
Primary ITP
▪ Severe ITP, fails to respond to/relapses after
▪ Idiopathic
splenectomy
Secondary ITP
▪ Caused by systemic condition RISK FACTORS
▪ Viral infections (most common) ▪ Age; genetic/acquired factors
▫ HIV, hepatitis C, cytomegalovirus
▫ Antibodies against viral antigens
cross-react with platelet antigens via
molecular mimicry
▪ Bacterial lipopolysaccharides attach to
platelet surfaces → increase phagocytosis
of platelets
▪ Systemic lupus erythematosus, lymphoid
OSMOSIS.ORG 457
COMPLICATIONS
▪ Potentially severe hemorrhage (uncommon)
TREATMENT
▫ Intracranial bleeding, subarachnoid
MEDICATIONS
hemorrhage, gastrointestinal (GI)
hemorrhage, hematuria, severe Raise platelet count
menorrhagia ▪ High dose glucocorticoids (dexamethasone;
prednisone)
SIGNS & SYMPTOMS ▪ Immune globulin (IVIG)
If no response to above medications
▪ Bruising easily after minor trauma ▪ Rituximab
▪ Mucocutaneous bleeding ▫ Monoclonal antibody reduces antibody-
▫ Petechiae, purpura, epistaxis, gingival dependent cytotoxicity, complement-
bleeding mediated lysis of platelets
▪ Thrombopoietin (TPO) receptor agonists
(e.g. eltrombopag)
DIAGNOSIS
▫ Increases platelet production
by stimulating production of
LAB RESULTS megakaryocytes
▪ CBC
▪ Immunosuppressive agents
▫ Low platelet count
▫ Danazol, azathioprine, cyclosporine
▪ Peripheral blood smear analysis
▫ Scarce platelets Medications to avoid
▪ Flow cytometry-based assays ▪ Antiplatelet agents
▫ Drug-dependent platelet antibodies ▫ Aspirin, other nonsteroidal anti-
inflammatory drugs (NSAIDs)
OTHER DIAGNOSTICS
▪ History of drug implicated in DITP SURGERY
▪ If no response to medication
Splenectomy
▪ Reduces platelet destruction
OTHER INTERVENTIONS
▪ Platelet transfusions
▫ Clinically significant bleeding
Figure 59.1 Multiple petechiae present in the
skin of an individual with ITP. The platelet
count was < 5 x 109/L.
458 OSMOSIS.ORG
Chapter 59 Thrombocytopenia
THROMBOTIC
THROMBOCYTOPENIC PURPURA
(TTP)
osms.it/thrombotic-thrombocytopenic
ancestry, diagnosed with systemic lupus
PATHOLOGY & CAUSES erythematosus (SLE)
▪ Sepsis, liver disease, pancreatitis, cardiac
▪ Thrombotic microangiopathy (TMA) surgery
caused by deficient activity of ADAMTS13
▫ Reduce activity of ADAMTS13
protease
▪ Pregnancy
▪ ADAMTS13 breaks von Willebrand factor
(vWF) molecules into smaller multimers, ▫ Decrease in ADAMTS13, increase in
prevents excessive accumulation on vWF, 2nd–3rd trimesters
endothelial surfaces in microvasculature
▪ Excessive vWF on endothelial surfaces → COMPLICATIONS
increased propensity for platelets to attach, ▪ Organ damage
accumulate (esp. in high pressure areas ▫ Renal insufficiency, focal neurologic/
with shearing stress) + endothelial damage mental status anomalies, arrhythmias
→ platelet-rich thrombi in microcirculation
→ tissue ischemia, organ dysfunction,
microangiopathic hemolytic anemia SIGNS & SYMPTOMS
(MAHA), thrombocytopenia
▪ Thrombocytopenia consumptive ▪ Classic TTP pentad
▫ Increased need for platelets from cyclical ▫ Thrombocytopenia, MAHA, renal
clot formation, dissolution dysfunction, neurologic impairment (e.g.
▪ MAHA headache, confusion, seizures, coma),
▫ Red blood cell (RBC) mechanical fever
fragmentation in microthrombi, ▪ Mucocutaneous bleeding
damaged vessels → schistocytes ▫ Petechiae, purpura (coalesced
▪ Organs most affected by TTP in petechiae), epistaxis, gingival bleeding
microcirculation ▪ Intravascular hemolysis → dark urine
▫ Brain, heart, adrenal glands, pancreas, ▪ Lightheadedness, abdominal pain, easy
kidneys bruising, nausea/vomiting
CAUSES
▪ ADAMTS13 deficiency
MNEMONIC: RAFT'N
Common signs of Thrombotic
▫ Acquired inhibitory autoantibody (IgG)
thrombocytopenia purpura
to ADAMTS13; inherited mutation of
ADAMTS13 gene (minority) Renal problems
Anemia: MAHA associated
Fever
RISK FACTORS
Thrombocytopenia
▪ Increased prevalence in individuals
who are biologically female, of African Neurologic dysfunction
OSMOSIS.ORG 459
OTHER DIAGNOSTICS
DIAGNOSIS ▪ ADAMTS13 assay
▫ Gel electrophoresis of VWF multimers
LAB RESULTS
measures degradation by ADAMTS13
▪ CBC
▪ ADAMTS13 inhibitor assay
▫ Decreased platelet count
▫ Autoantibody titer
▫ Increased reticulocyte count
▪ Genetic testing
▫ Decreased hemoglobin, hematocrit
▫ ADAMTS13 gene mutation, if hereditary
▪ Peripheral blood smear analysis TTP suspected
▫ Schistocytes, spherocytes
▪ Hemolysis
▫ Elevated lactate dehydrogenase (LDH) TREATMENT
▫ Elevated indirect bilirubin
▫ Reduced haptoglobin
MEDICATIONS
▪ Glucocorticoids
▪ Elevated creatinine
▪ Monoclonal antibody
▫ Renal insufficiency
OTHER INTERVENTIONS
▪ Plasma exchange (PEX)
460 OSMOSIS.ORG
