What is the diagnosis and treatment for a 54-year-old non-hypertensive female with diabetic ketoacidosis (DKA), status post (s/p) cardiac arrest (CP arrest) with 3 minutes of downtime, who became hypotensive, has progressive deterioration of level of consciousness, multiple intracerebral hemorrhages on cranial computed tomography (CT) scan, severe thrombocytopenia (platelet count of 18), impaired renal function (elevated creatinine), and hypernatremia (elevated sodium)?

Diagnosis: Thrombotic Thrombocytopenic Purpura (TTP) Complicating Diabetic Ketoacidosis

This patient most likely has thrombotic thrombocytopenic purpura (TTP) as a rare but life-threatening complication of her diabetic ketoacidosis, evidenced by the classic pentad: severe thrombocytopenia (platelet count 18), neurological deterioration, renal dysfunction (elevated creatinine), multiple intracerebral hemorrhages, and the clinical context of DKA with cardiac arrest. 1

Clinical Reasoning

The constellation of findings strongly suggests TTP rather than simple coagulopathy from DKA:

• Severe thrombocytopenia (18,000/μL) with multiple intracerebral hemorrhages and progressive neurological deterioration despite initial resuscitation from cardiac arrest points to a microangiopathic process 1
• Elevated creatinine indicates acute kidney injury, which is part of the TTP pentad 1
• The post-cardiac arrest state with hypotension may have triggered or worsened the thrombotic microangiopathy 1
• Hypernatremia is consistent with severe dehydration from DKA and potential diabetes insipidus from neurological injury 2, 3

TTP secondary to DKA is rare but carries significant mortality if untreated, and the combination of thrombocytopenia, renal failure, and reduced consciousness in the setting of DKA should immediately raise suspicion for this diagnosis 1

Immediate Medical Treatment

1. Urgent Plasmapheresis (Plasma Exchange)

Initiate plasmapheresis immediately without waiting for ADAMTS13 results, as this is the definitive life-saving treatment for TTP with mortality reduction from 90% to 10-20% when started promptly 1

• Perform daily plasma exchange (1-1.5 plasma volumes) until platelet count normalizes and neurological symptoms improve 1
• Continue for at least 2 days after platelet count exceeds 150,000/μL 1

2. Concurrent DKA Management

Fluid resuscitation: Begin with isotonic saline at 15-20 mL/kg/hour for the first hour, then adjust based on hemodynamic status and corrected sodium 2, 3

Insulin therapy: Start continuous IV regular insulin at 0.1 units/kg/hour after confirming potassium ≥3.3 mEq/L 2, 3

• Target glucose decline of 50-75 mg/dL per hour 2
• When glucose reaches 200-250 mg/dL, add 5% dextrose to IV fluids while continuing insulin to resolve ketoacidosis 2, 4
• Do NOT stop insulin until DKA resolves (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) 2, 3, 4

Electrolyte management:

• Critical: If potassium <3.3 mEq/L, delay insulin and aggressively replace potassium first to prevent fatal arrhythmias 3
• Once potassium ≥3.3 mEq/L and urine output confirmed, add 20-30 mEq/L potassium to IV fluids (2/3 KCl, 1/3 KPO₄) 2, 3, 4
• Target serum potassium 4-5 mEq/L throughout treatment 3, 4
• Monitor potassium every 2-4 hours as insulin drives it intracellularly 2, 3

Bicarbonate: Do NOT administer bicarbonate unless pH <6.9, as it provides no benefit and may worsen outcomes 3, 4

3. Platelet Transfusion Contraindication

Avoid platelet transfusions in TTP as they may worsen thrombosis and neurological deterioration; only transfuse for life-threatening bleeding 1

4. Supportive Care for Intracerebral Hemorrhage

• Maintain systolic blood pressure <140 mmHg to prevent hematoma expansion (once hemodynamically stable from DKA) 5
• Elevate head of bed 30 degrees 5
• Neurosurgical consultation for potential need for intracranial pressure monitoring or surgical intervention 5
• Avoid antiplatelet agents and anticoagulation 5

5. Treatment of Precipitating Factors

Identify and treat underlying infection or other DKA triggers with appropriate antibiotics if infection suspected 2, 3, 6

Additional Diagnostic Tests

Immediate (Stat) Tests:

• ADAMTS13 activity level (send before plasmapheresis but do not delay treatment) - activity <10% confirms TTP 1
• Peripheral blood smear - look for schistocytes (fragmented RBCs) indicating microangiopathic hemolytic anemia 1
• Lactate dehydrogenase (LDH) - typically markedly elevated in TTP 1
• Direct and indirect Coombs test - negative in TTP (helps exclude autoimmune hemolytic anemia) 1
• Haptoglobin - typically low/undetectable due to hemolysis 1
• Reticulocyte count - elevated due to hemolysis 1
• Arterial blood gas - to monitor DKA resolution (pH, bicarbonate) 2, 3, 4
• Serum beta-hydroxybutyrate - preferred over urine ketones for monitoring DKA 2, 4

Every 2-4 Hours During Active Treatment:

• Venous pH, electrolytes (including calcium and magnesium), glucose, BUN, creatinine, anion gap 2, 3, 4
• Complete blood count with platelet count 1

Additional Workup:

• Blood and urine cultures if infection suspected as DKA precipitant 2, 3, 6
• Troponin and ECG - cardiac arrest may have been precipitated by myocardial infarction 3, 6
• CT angiography of brain - to evaluate for underlying vascular abnormalities or ongoing bleeding 5
• Urinalysis - assess for proteinuria and hematuria (renal involvement in TTP) 2, 3

Monitoring Parameters

• Neurological status: Hourly Glasgow Coma Scale and pupillary examination 1, 5
• Platelet count: Every 12 hours initially, then daily once improving 1
• Glucose: Every 1-2 hours during active DKA treatment 2, 3
• Electrolytes and renal function: Every 2-4 hours until DKA resolves 2, 3, 4
• Hemodynamic parameters: Continuous monitoring given post-cardiac arrest state and hypotension 2, 3

Critical Pitfalls to Avoid

• Delaying plasmapheresis while waiting for ADAMTS13 results - this is fatal; start immediately when TTP is suspected 1
• Transfusing platelets in TTP - contraindicated except for life-threatening bleeding 1
• Stopping insulin when glucose normalizes - continue until ketoacidosis fully resolves (pH >7.3, bicarbonate ≥18 mEq/L) 2, 3, 4
• Starting insulin with potassium <3.3 mEq/L - can cause fatal cardiac arrhythmias 3
• Attributing neurological deterioration solely to cerebral edema - in this case with severe thrombocytopenia and hemorrhages, TTP is the primary concern 1, 5
• Premature discontinuation of IV insulin without administering basal subcutaneous insulin 2-4 hours prior - causes rebound ketoacidosis 2, 3, 4

Prognosis

With prompt plasmapheresis, neurological recovery is possible even with intracerebral hemorrhages, though outcomes are generally guarded 1, 5. The case report of a pediatric patient with similar presentation showed complete recovery after plasmapheresis initiated within 48 hours 1.