How do you differentiate and manage Thrombotic Thrombocytopenic Purpura (TTP) vs Disseminated Intravascular Coagulation (DIC)?

Differentiating and Managing TTP vs DIC

TTP and DIC can be rapidly distinguished by three key laboratory parameters: severe thrombocytopenia (<20×10⁹/L), normal antithrombin levels (>87%), and mildly elevated FDP (<23 µg/mL) strongly suggest TTP over DIC. 1

Critical Diagnostic Distinctions

Laboratory Differentiation

Platelet Count:

• TTP presents with more severe thrombocytopenia (typically <20×10⁹/L) compared to DIC 1
• In DIC, platelet counts are moderately reduced but rarely as profoundly low as in TTP 2

Coagulation Parameters:

• PT/INR and aPTT are normal or minimally prolonged in TTP, whereas they are significantly prolonged in DIC 1
• Antithrombin levels remain normal (>87%) in TTP but are markedly decreased in DIC 1
• Fibrinogen is typically normal in TTP but consumed and low in DIC 2

Fibrinolysis Markers:

• Both conditions show elevated D-dimer and FDP, but DIC demonstrates significantly higher levels 1
• FDP <23 µg/mL favors TTP over DIC 1

ADAMTS13 Activity:

• Severe ADAMTS13 deficiency (<10%) is pathognomonic for TTP and absent in DIC 3, 4
• This test should be sent immediately but treatment should not be delayed awaiting results 5, 6

Clinical Context

TTP typically presents with:

• Microangiopathic hemolytic anemia with schistocytes 4
• Neurological symptoms (altered mental status, seizures) 6, 4
• Renal dysfunction (less severe than in DIC) 6
• Absence of sepsis, infection, or other DIC triggers 3

DIC occurs in the context of:

• Sepsis, trauma, malignancy, or obstetric complications 2
• Multi-organ dysfunction with hepatic involvement 2
• Active bleeding or thrombosis 2

Management Algorithms

TTP Management

Immediate Treatment (Do Not Delay):

• Initiate daily therapeutic plasma exchange (TPE) immediately upon clinical suspicion, even before ADAMTS13 results return 5, 6
• Continue TPE daily until platelet count >150×10⁹/L and LDH normalizes for 2-3 consecutive days 3, 5
• Median treatment duration is approximately 35 days 3

Adjunctive Immunosuppression:

• Add corticosteroids to TPE 6, 4
• Consider rituximab (anti-CD20 antibody) for refractory cases or to prevent relapse 4

Novel Therapy:

• Caplacizumab (11 mg IV bolus, then 11 mg SC daily) in combination with TPE and immunosuppression significantly reduces time to platelet recovery and TTP recurrence (13% vs 38% recurrence rate, p<0.001) 3
• Caplacizumab should be continued for 30 days after stopping TPE, with possible extension if ADAMTS13 activity remains <10% 3

Critical Pitfall: Stopping TPE prematurely when ADAMTS13 activity remains <10% leads to high relapse rates 3, 5

DIC Management

Treat the Underlying Cause First:

• Management of the underlying condition (sepsis, malignancy, trauma) is the cornerstone of DIC treatment 2, 7
• Early recognition using ISTH DIC scoring or SIC criteria facilitates timely intervention 2

Hemostatic Support (Threshold-Based):

• Active bleeding: Maintain platelets >50×10⁹/L 2, 7
• High bleeding risk without active bleeding: Transfuse platelets if <30×10⁹/L (APL) or <20×10⁹/L (other cancers) 2
• Fresh frozen plasma: 15-30 mL/kg for active bleeding with prolonged PT/aPTT 2, 7
• Fibrinogen replacement: If <1.5 g/L despite FFP, give cryoprecipitate (2 pools) or fibrinogen concentrate 2, 7

Anticoagulation Strategy:

• Heparin is indicated primarily for thrombotic-predominant DIC (not bleeding-predominant) 7
• Contraindications: Active bleeding, platelets <20×10⁹/L, hyperfibrinolytic DIC 7, 8
• Unfractionated heparin preferred in renal failure or high bleeding risk due to reversibility 7, 8
• LMWH preferred in other cases for convenience 7

Monitoring:

• Daily monitoring minimum of CBC, PT/aPTT, fibrinogen, and D-dimer in acute DIC 2, 8
• A 30% drop in platelet count may indicate subclinical DIC progression 2

Key Pitfalls to Avoid

In TTP:

• Never delay TPE waiting for ADAMTS13 results - mortality is extremely high without immediate treatment 6, 4
• Do not stop treatment based solely on platelet recovery - ensure ADAMTS13 activity has recovered to prevent relapse 3, 5
• Avoid platelet transfusions in TTP unless life-threatening bleeding, as they may worsen microthrombosis 4

In DIC:

• Do not transfuse prophylactically based on laboratory values alone without bleeding or high-risk procedures 7, 9
• Recognize that normal platelet counts do not exclude DIC in patients with baseline thrombocytosis from malignancy - look for decreasing trends 2
• PT/aPTT may be normal in early or cancer-associated DIC - do not rely solely on these tests 2

Critical Distinction:

• Patients with sepsis, E. coli O157 infection, or disseminated intravascular coagulation were specifically excluded from TTP trials 3, highlighting that these conditions represent DIC, not TTP, and require fundamentally different management approaches.