How to manage a patient with psychosis and thrombocytosis?

Management of Psychosis with Thrombocytosis

Immediate Priority: Rule Out Life-Threatening Secondary Causes

The first critical step is to distinguish whether psychosis is primary psychiatric versus secondary to a medical condition, as approximately 20% of acute psychosis cases have an underlying medical etiology that requires specific treatment. 1 This distinction fundamentally changes management and directly impacts mortality and morbidity.

Key Diagnostic Differentiation

Evaluate immediately for delirium versus psychosis - this is the most critical pitfall that doubles mortality if missed:

• Delirium: fluctuating consciousness, disorientation, inattention, acute onset over hours to days 2, 3
• Psychosis: intact awareness and level of consciousness, with delusions, hallucinations, disorganized speech 3, 4

Essential History and Physical Examination Elements

Focus your evaluation on these specific high-yield findings:

Vital Signs (abnormal vitals suggest medical cause):

• Tachycardia or severe hypertension → drug toxicity or thyrotoxicosis 4
• Fever → encephalitis, porphyria, or systemic infection 4, 2

Neurological Examination:

• Focal deficits → structural brain lesion requiring urgent imaging 3
• Asterixis and myoclonus → metabolic encephalopathy 3
• Assess for catatonia, agitation, or abnormal movements 3

Critical History Points:

• Recent head trauma → traumatic brain injury 2, 4
• Seizures or new/worsening headaches → CNS pathology 4
• Medication review → drug-induced psychosis or withdrawal states 5, 3
• Illicit drug use → most common medical cause of acute psychosis 4

Thrombocytosis Considerations

The presence of thrombocytosis alongside psychosis raises specific diagnostic possibilities:

Systemic Lupus Erythematosus (SLE) with Neuropsychiatric Manifestations

If SLE is suspected or known, consider antiphospholipid antibody syndrome, which creates a fivefold increased risk for neuropsychiatric manifestations including psychosis 5:

• Check antiphospholipid antibodies and anticardiolipin antibodies - these are strongly associated with both thrombocytosis and psychotic manifestations 5, 6
• Lupus psychosis is rare but requires specific treatment 5
• Major depression attributed to SLE alone is relatively uncommon while psychosis is rare 5

Prothrombotic State in Acute Psychosis

Emerging evidence shows that acute psychosis itself activates thrombogenic markers (D-dimers, Factor VIII, soluble P-selectin) independent of antipsychotic medication 7. This suggests:

• Thrombocytosis may be reactive to the psychotic state itself
• Venous thromboembolic risk is elevated even before antipsychotic treatment 7

Diagnostic Workup Algorithm

Laboratory Testing

Initial laboratory panel (indicated when new-onset psychosis, acute changes, or concerning findings on history/physical) 5, 4:

• Complete blood count (confirms thrombocytosis)
• Comprehensive metabolic panel
• Thyroid function tests
• Calcium and parathyroid hormone
• Vitamin B12, folate, niacin
• Urine toxicology screen
• HIV and syphilis testing (consider)

For thrombocytosis specifically:

• Antiphospholipid antibodies and anticardiolipin antibodies 5, 6
• Lupus anticoagulant 6
• ANA and anti-dsDNA if SLE suspected 6

Neuroimaging

Obtain brain MRI (preferred) or CT if 2, 3:

• Focal neurological deficits present
• History of head trauma
• New-onset psychosis in elderly patients
• First episode psychosis with neurological signs
• Atypical features or symptoms not responding to management

MRI protocol should include: T1/T2, FLAIR, diffusion-weighted imaging (DWI), and gadolinium-enhanced T1 sequences 5

Additional Testing Based on Clinical Suspicion

• Lumbar puncture with CSF analysis - to exclude CNS infection, especially if fever, altered mental status, or meningeal signs 5
• EEG - if seizure disorder suspected 5
• Brain SPECT - may be considered in severe cases when standard workup fails to reveal cause (93% sensitivity for lupus-related acute confusional states) 5

Treatment Approach

If SLE-Related Psychosis with Antiphospholipid Antibodies

Glucocorticoids and immunosuppressive therapy (usually cyclophosphamide, followed by maintenance with azathioprine) should be considered in SLE-associated psychosis, especially in presence of generalized disease activity 5:

• Response rates: 60-80% 5
• Most psychiatric episodes resolve within 2-4 weeks 5
• Relapses may occur in up to 50% 5

Anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly in thrombotic manifestations 5:

• Antiplatelet agents (aspirin 100 mg daily) for primary prevention with persistently positive moderate/high antiphospholipid antibody titers 5, 6
• Consider hydroxychloroquine as adjunctive therapy 6

If Primary Psychiatric Psychosis

Initiate atypical antipsychotic immediately 8:

• Risperidone 2-4 mg/day or olanzapine 10-15 mg/day as first-line options 8
• Avoid large initial doses - they increase side effects without hastening recovery 3, 8
• Implement treatment for 4-6 weeks before determining efficacy 3
• Antipsychotic effects typically become apparent after 1-2 weeks 3

Symptomatic therapies should also be considered: anticonvulsants if seizures, antidepressants if mood component 5

Critical Management Pitfalls to Avoid

1. Don't overlook withdrawal states - alcohol or benzodiazepine withdrawal can cause both psychosis and life-threatening seizures requiring immediate benzodiazepine treatment 3

2. Don't delay neuroimaging when focal neurological signs, head trauma history, or atypical features are present 3

3. Don't assume thrombocytosis is unrelated - it may indicate underlying SLE/antiphospholipid syndrome requiring specific immunosuppressive and anticoagulation therapy 5, 6

4. Don't treat with antipsychotics alone if antiphospholipid syndrome is present - combined treatment with antipsychotics, aspirin, and antimalarials is recommended 6

Disposition and Follow-up

Include families in the treatment plan and provide them with emotional support and practical advice 3, 8

Maintain continuity of care with the same treating clinicians for at least the first 18 months of treatment 3

All patients with first episode psychosis for which no organic cause can be found should be referred to the local early intervention service 9