Treatment of Intracerebral Hemorrhage in Thrombotic Thrombocytopenic Purpura
In a patient with TTP who develops intracerebral hemorrhage, immediately initiate or continue therapeutic plasma exchange (TPE) with corticosteroids and rituximab, while avoiding platelet transfusions which can worsen thrombosis. 1
Critical Distinction: TTP is NOT ITP
TTP requires fundamentally different management than immune thrombocytopenic purpura (ITP). 2 While ITP involves autoimmune platelet destruction treated with corticosteroids and immunosuppression to raise platelet counts, TTP is a thrombotic microangiopathy caused by ADAMTS-13 deficiency requiring urgent plasma-based therapy. 2 Platelet transfusions are contraindicated in TTP as they can precipitate further microvascular thrombosis and worsen outcomes. 1
Immediate Management Protocol
Primary Treatment for TTP with ICH
Continue or initiate therapeutic plasma exchange (TPE) immediately as the cornerstone of TTP treatment, even in the presence of intracerebral hemorrhage. 1 TPE removes the pathogenic anti-ADAMTS-13 antibodies and replaces the deficient ADAMTS-13 enzyme.
Add caplacizumab to the treatment regimen (TPE, corticosteroids, and rituximab) as it provides therapeutic efficacy and potential survival benefit in iTTP. 1 However, be aware that fatal intracerebral hemorrhage has been reported in a TTP patient with normalized platelet count during caplacizumab treatment, though this is extremely rare. 3
Administer high-dose corticosteroids (typically prednisone 1 mg/kg/day or equivalent methylprednisolone) in conjunction with TPE. 1
Initiate rituximab as part of the standard treatment protocol for immune TTP. 1
Critical Care Measures
Provide conventional critical care support including airway management, blood pressure control, and neurological monitoring as you would for any intracerebral hemorrhage. 4
Monitor neurological status closely with serial examinations every 15-30 minutes initially, then hourly, watching for signs of increased intracranial pressure, altered mental status, focal deficits, or seizures. 4, 5
Obtain urgent head CT imaging to characterize the hemorrhage location, size, and any mass effect requiring neurosurgical intervention. 5
What NOT to Do
Avoid Platelet Transfusions
Do not transfuse platelets in TTP unless there is life-threatening hemorrhage requiring emergency neurosurgical intervention. 1 Platelet transfusions in TTP can precipitate further microvascular thrombosis and worsen the underlying disease process. This is the opposite of ITP management, where platelet transfusions combined with IVIg are appropriate for ICH. 4, 5
Avoid ITP-Specific Treatments
Do not use IVIg as the primary treatment, as this is appropriate for ITP but not TTP. 4, 5
Do not use thrombopoietin receptor agonists or other ITP-specific therapies. 6
Special Considerations for Congenital TTP
If the patient has congenital (hereditary) TTP rather than immune TTP:
Use recombinant ADAMTS-13 replacement therapy as the preferred treatment over fresh frozen plasma, based on strong recommendation with moderate certainty evidence. 1
If recombinant ADAMTS-13 is unavailable, use fresh frozen plasma for ADAMTS-13 replacement rather than a watch-and-wait approach. 1
Emergency treatment may include exchange transfusion in addition to plasma therapy to arrest the intravascular thrombotic process, particularly in infants or young children. 7
Antithrombotic Management
The 2025 ISTH guidelines include good practice statements on concomitant antithrombotic agents, though specific details require shared decision-making based on the balance of thrombotic versus bleeding risk in the individual patient. 1 Given the presence of ICH, hold antithrombotic agents during the acute hemorrhagic phase unless there is a compelling indication.
Prognosis and Monitoring
ICH in the setting of TTP carries significant mortality risk, though specific mortality data for TTP-associated ICH is limited in the literature. 3, 7
Continue TPE daily until platelet count normalization and suppression of hemolysis markers, typically requiring 5-7 days or longer. 1
Monitor ADAMTS-13 activity levels to guide duration of therapy and assess for relapse risk. 1
Common Pitfalls
Mistaking TTP for ITP: Look for schistocytes on peripheral smear and evidence of microangiopathic hemolytic anemia (MAHA) to distinguish TTP from ITP. 6 The presence of hemolysis, renal dysfunction, and neurological symptoms in addition to thrombocytopenia suggests TTP rather than ITP.
Transfusing platelets reflexively: This can be catastrophic in TTP by worsening microvascular thrombosis. 1
Delaying plasma exchange: TPE should be initiated emergently when TTP is suspected, even before ADAMTS-13 results return. 1
Assuming normal platelet count means safety from bleeding: The fatal case of ICH during caplacizumab treatment occurred despite platelet count recovery, highlighting that bleeding risk persists even with normalized counts. 3