Clinical Conditions Associated with MAHA Blood picture: Thrombotic Thrombocytopenic Purpura (TTP), Hemolytic Uremic Syndrome (HUS), Disseminated Intravascular Coagulation (DIC), and HELLP Syndrome
- Mayta
- Sep 10, 2024
- 5 min read
A table recapping the clinical conditions associated with MAHA:
Feature | Thrombotic Thrombocytopenic Purpura (TTP) | Hemolytic Uremic Syndrome (HUS) | Disseminated Intravascular Coagulation (DIC) |
History (Signs & Symptoms) | Fatigue, pallor, petechiae, neurological symptoms, fever, jaundice | Fatigue, pallor, diarrhea (bloody), abdominal pain, vomiting, decreased urine output | Bleeding from IV sites, mucosal bleeding, bruising, signs of organ failure |
Physical Examination | Pallor, jaundice, petechiae, neurological deficits, tachycardia | Pallor, jaundice, petechiae, dehydration, oliguria or anuria | Petechiae, purpura, oozing from IV sites, tachycardia, hypotension, multi-organ failure |
Diagnosis Criteria | ADAMTS13 activity <10%, schistocytes ≥1%, platelet <30,000/μL, normal coagulation profile | Triad: Hemolytic anemia, thrombocytopenia, acute kidney injury | ISTH DIC score ≥5, platelet <100,000/μL, prolonged PT, elevated D-dimer, fibrinogen <100 mg/dL |
Lab Findings | Schistocytes, platelet <30,000/μL, LDH >1000 U/L, normal PT/aPTT | Schistocytes, platelet 10,000-50,000/μL, elevated creatinine, LDH >600 U/L | Schistocytes, platelet <100,000/μL, elevated D-dimer, prolonged PT/aPTT, fibrinogen <100 mg/dL |
Management | Plasma exchange, corticosteroids, caplacizumab, rituximab | Supportive care, dialysis, avoid antibiotics (Shiga toxin), eculizumab for atypical HUS | Treat underlying cause, blood products (FFP, platelets), cryoprecipitate, anticoagulation (if thrombosis) |
Introduction
Clinical Conditions Associated with MAHA:
To approach this at the depth required for internal medicine residents, we'll break down each condition into History Taking (signs and symptoms), Physical Examination Findings, Criteria for Diagnosis (with exact numbers), Laboratory Investigations (with specific values), and Management (including treatment orders).
1. Thrombotic Thrombocytopenic Purpura (TTP)
History Taking:
Fatigue, pallor (due to anemia)
Petechiae, purpura, mucosal bleeding (due to thrombocytopenia)
Neurological symptoms: confusion, headache, seizures, transient ischemic attacks (TIA), stroke-like symptoms.
Fever (non-specific)
Oliguria or hematuria (rare but indicates renal involvement)
Jaundice (due to hemolysis)
Physical Examination:
Pallor, jaundice
Petechiae, purpura, bruising
Neurological deficits: motor or sensory abnormalities
Tachycardia (due to anemia)
Mild to moderate hypertension (if present)
Criteria for Diagnosis:
ADAMTS13 activity: <10% confirms TTP.
Diagnosis is based on a combination of clinical findings and laboratory evidence of MAHA and thrombocytopenia, with the presence or absence of ADAMTS13 deficiency.
Laboratory Investigations:
Platelet count: <30,000/μL (severe thrombocytopenia).
Hemoglobin: low, typically <10 g/dL.
Schistocytes: ≥1% of red blood cells on a peripheral blood smear.
LDH: significantly elevated, often >1,000 U/L (due to hemolysis).
Haptoglobin: decreased (<25 mg/dL).
Reticulocyte count: elevated, typically >2.5% (due to hemolysis).
Coagulation profile (PT, aPTT): normal (helps distinguish from DIC).
ADAMTS13 assay: <10% activity confirms diagnosis.
Management:
Plasma Exchange (PEX):
Order: Fresh frozen plasma exchange 1.5 times plasma volume daily until platelet count >150,000/μL and LDH normalizes.
Corticosteroids:
Order: Prednisone 1 mg/kg/day PO (oral), typically continued for 1-2 weeks then tapered.
Caplacizumab (anti-VWF therapy):
Order: Caplacizumab 10 mg IV bolus before plasma exchange, then 10 mg SC daily for 30 days after cessation of PEX.
Rituximab (if refractory):
Order: Rituximab 375 mg/m² IV weekly for 4 doses.
Platelet transfusions are contraindicated unless there is a life-threatening hemorrhage.
2. Hemolytic Uremic Syndrome (HUS)
History Taking:
Diarrheal illness, often bloody, preceding the onset of symptoms by 5-10 days (Shiga toxin-producing E. coli).
Fatigue, pallor (due to anemia).
Decreased urine output, hematuria, or dark urine (renal involvement).
Abdominal pain, vomiting, and fever.
Neurological symptoms (in severe cases): irritability, seizures, confusion.
Physical Examination:
Pallor, jaundice (due to hemolysis).
Petechiae, purpura (due to thrombocytopenia).
Dehydration signs (due to diarrhea).
Oliguria or anuria (in severe cases).
Hypertension (due to acute kidney injury).
Criteria for Diagnosis:
Triad of HUS:
Microangiopathic hemolytic anemia (schistocytes).
Thrombocytopenia.
Acute kidney injury (AKI).
Laboratory Investigations:
Platelet count: typically 10,000–50,000/μL.
Hemoglobin: low, typically <10 g/dL.
Schistocytes: ≥1% on peripheral smear.
LDH: elevated, usually >600 U/L.
Haptoglobin: decreased (<25 mg/dL).
Serum creatinine: elevated, often >2 mg/dL (indicating AKI).
Stool culture/PCR: positive for Shiga toxin (if related to E. coli).
Coagulation profile: normal (unlike DIC).
Management:
Supportive care:
Order: IV fluids, electrolyte management.
Dialysis (if AKI is severe):
Order: Hemodialysis or peritoneal dialysis as needed based on renal function.
Avoid antibiotics in Shiga toxin-associated HUS, as they may worsen the condition.
Eculizumab (for atypical HUS):
Order: Eculizumab 900 mg IV weekly for 4 weeks, then 1,200 mg IV every 2 weeks.
3. Disseminated Intravascular Coagulation (DIC)
History Taking:
Bleeding: from mucous membranes (gums, nose), IV sites, surgical wounds.
Bruising, petechiae, purpura.
Fatigue, dyspnea, chest pain.
Signs of organ dysfunction: confusion (CNS involvement), oliguria (kidney), dyspnea (lungs).
Triggering event: sepsis, trauma, cancer, or obstetric emergencies (e.g., placental abruption).
Physical Examination:
Petechiae, purpura, ecchymosis.
Oozing from IV sites or wounds.
Tachycardia, hypotension (shock in severe cases).
Signs of multi-organ failure: altered mental status, renal failure, respiratory distress.
Criteria for Diagnosis:
Based on ISTH (International Society of Thrombosis and Hemostasis) DIC score (≥5 points suggests overt DIC):
Platelet count: <100,000/μL (1 point if 50,000-100,000; 2 points if <50,000).
D-dimer: elevated (>1 mg/L) (1 point for moderate increase; 2 points for strong increase).
PT prolongation: >3 seconds (1 point for 3-6 seconds; 2 points for >6 seconds).
Fibrinogen: <100 mg/dL (1 point).
Laboratory Investigations:
Platelet count: <100,000/μL.
PT: prolonged by >3 seconds.
aPTT: prolonged (>35 seconds).
D-dimer: markedly elevated (>1 mg/L).
Fibrinogen: decreased, typically <100 mg/dL.
Schistocytes: present on peripheral smear.
LDH: elevated, often >1,000 U/L.
Haptoglobin: decreased.
Management:
Treat underlying cause:
Order: IV antibiotics for sepsis, surgery for trauma, etc.
Blood products:
Order: Fresh Frozen Plasma (FFP) 10-15 mL/kg IV, platelets if <20,000/μL with active bleeding.
Cryoprecipitate:
Order: Cryoprecipitate 10 units to increase fibrinogen.
Anticoagulation (heparin):
Order: Heparin unfractionated heparin drip, 5000 units bolus followed by continuous infusion, only if thrombosis predominates and no active bleeding.
4. HELLP Syndrome
History Taking:
Occurs in pregnancy, usually in the third trimester.
Right upper quadrant or epigastric pain.
Nausea, vomiting, malaise.
Headache, blurred vision, scotoma (in preeclampsia).
Jaundice, fatigue (due to hemolysis).
History of preeclampsia or gestational hypertension.
Physical Examination:
Hypertension: typically >140/90 mmHg.
Right upper quadrant tenderness (liver involvement).
Jaundice.
Petechiae, purpura (due to thrombocytopenia).
Criteria for Diagnosis:
Hemolysis:
LDH >600 U/L, or total bilirubin >1.2 mg/dL.
Presence of schistocytes on blood smear.
Elevated liver enzymes:
AST >70 U/L.
Low platelets:
Platelet count <100,000/μL.
Laboratory Investigations:
Platelet count: <100,000/μL.
AST/ALT: elevated, often >70 U/L.
LDH: elevated, typically >600 U/L.
Peripheral blood smear: schistocytes.
Total bilirubin: >1.2 mg/dL.
Coagulation profile: normal to mildly prolonged.
Management:
Immediate delivery:
Order: Delivery is the definitive treatment once maternal and fetal stabilization is achieved.
Magnesium sulfate (for seizure prophylaxis in preeclampsia):
Order: Magnesium sulfate 4-6 g IV loading dose, followed by 2 g/hour maintenance infusion.
Antihypertensives:
Order: Labetalol 20 mg IV bolus, titrated every 10 minutes to a max of 300 mg, or hydralazine 5-10 mg IV.
Corticosteroids (for fetal lung maturity if preterm):
Order: Betamethasone 12 mg IM every 24 hours for two doses.
5. Malignant Hypertension
History Taking:
Severe headache, blurred vision, chest pain.
Dyspnea, palpitations, fatigue.
Confusion, seizures, altered mental status.
Hematuria, oliguria (due to kidney injury).
History of poorly controlled hypertension.
Physical Examination:
Severe hypertension: typically >180/120 mmHg.
Retinal hemorrhages, cotton wool spots, papilledema (hypertensive retinopathy).
Heart failure signs: crackles, JVP elevation, peripheral edema.
Neurological deficits: confusion, seizures.
Criteria for Diagnosis:
BP >180/120 mmHg with evidence of end-organ damage (e.g., encephalopathy, acute kidney injury, heart failure).
Laboratory Investigations:
Serum creatinine: elevated, often >1.5 mg/dL (acute kidney injury).
Urinalysis: hematuria, proteinuria.
Peripheral blood smear: schistocytes.
LDH: elevated, typically >600 U/L.
Haptoglobin: decreased.
Management:
Immediate BP reduction:
Order: IV labetalol or sodium nitroprusside drip (start at 0.3 mcg/kg/min and titrate).
IV diuretics (if volume overload):
Order: Furosemide 40 mg IV.
Monitor BP and titrate medications to maintain a target BP reduction of no more than 25% within the first hour.
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