What are the recommendations for a patient with Thrombotic Thrombocytopenic Purpura (TTP) undergoing plasma exchange with plasma and albumin, where a colloid is added to attain target replacement volume?

Plasma Exchange in TTP: Replacement Fluid Recommendations

Direct Answer

For patients with TTP undergoing plasma exchange, fresh frozen plasma (FFP) should be the primary replacement fluid, not albumin alone or albumin with colloids. 1 While albumin can be combined with plasma to reduce plasma volume requirements, using albumin or colloids as the sole or primary replacement fluid is inappropriate because they lack ADAMTS13 enzyme, which is essential for treating the underlying pathophysiology of TTP. 1

Why Plasma Must Be the Primary Replacement Fluid

FFP contains the critical ADAMTS13 enzyme needed to cleave von Willebrand factor multimers, which is the fundamental therapeutic mechanism in TTP. 1 The American Society of Nephrology explicitly recommends FFP as the standard replacement fluid for plasma exchange in TTP. 1

• Synthetic colloids like hydroxyethyl starch (HemoCel) cannot be used as replacement fluid in TTP because they lack ADAMTS13 enzyme and coagulation factors present in plasma products. 1
• The European Society of Anaesthesiology states that hydroxyethyl starch is not suitable for TTP plasma exchange. 1

Acceptable Replacement Fluid Protocols

Standard Approach

• Use FFP as the sole replacement fluid at 1-1.5 plasma volumes daily until platelet count normalizes (≥150,000/µL). 1, 2
• Continue daily plasma exchange until serum LDH normalizes and platelet count recovers, then slowly taper. 2

Alternative Plasma-Based Options

• Cryoprecipitate-poor plasma (cryosupernatant) may be used as an alternative, as it is relatively deficient in large von Willebrand factor multimers. 1, 2
• Studies show no statistical difference in overall response or complete response rates between FFP and cryosupernatant plasma (p=0.25 and p=0.16, respectively). 2

Albumin-Plasma Combination Protocols

• Albumin can be combined with plasma to reduce total plasma volume requirements, but plasma must remain a substantial component. 3
• A protocol using albumin plus FFP (1:1 ratio) has demonstrated efficacy without increasing hemorrhage risk. 3
• An alternative protocol using albumin plus mixed plasma [albumin:FFP:cryoprecipitate-reduced plasma in 2:1:1 ratio] showed comparable efficacy with potentially fewer plasma exchanges required (median 4 vs. 6) and shorter time to response (median 15 vs. 31 days). 3

Treatment Algorithm

Immediate Initiation

• Start plasma exchange immediately when TTP is suspected—do not delay for ADAMTS13 results. 1
• The American College of Emergency Physicians advises against waiting for laboratory confirmation if the PLASMIC score indicates intermediate-to-high risk. 1

Concurrent Therapy

• Add high-dose glucocorticoids concurrently with plasma exchange. 1
• If patient fails to respond after approximately 7 exchanges with FFP, consider switching to cryosupernatant. 1
• For refractory cases or confirmed severe ADAMTS13 deficiency, add rituximab and/or caplacizumab. 1

Response Monitoring

• Primary endpoint is platelet count ≥150,000/µL followed by cessation of daily plasma exchange within 5 days. 4
• Overall response rates with plasma exchange range from 75-77%, with complete response rates of 57.9-74.2% depending on whether TTP is primary or secondary. 2

Critical Pitfalls to Avoid

Do Not Use Albumin or Colloids Alone

• Using albumin or synthetic colloids as the sole replacement fluid will fail to address the ADAMTS13 deficiency that defines TTP. 1
• This approach would be analogous to volume resuscitation without treating the disease mechanism.

Recognize Prognostic Factors

• Presence of fever is a statistically significant bad prognostic indicator (p<0.01), requiring prolonged treatment with plasma exchange. 2
• The number of plasma exchanges required is also a statistically important factor influencing probability of response (p<0.01). 2
• Primary TTP has significantly better complete response rates compared to secondary TTP (74.2% vs. 29.4%; p=0.005). 2

Avoid Unnecessary Delays

• Response to plasma exchange in TTP patients treated with caplacizumab showed median time to platelet response was significantly shortened compared to placebo. 4
• Exacerbations occur in 4.2% of patients treated with caplacizumab versus 38.4% with placebo during the 30-day post-plasma exchange period. 4

Evidence Quality Considerations

The recommendation for plasma-based replacement fluids is supported by high-quality guideline evidence from the American Society of Nephrology and International Society of Nephrology. 1 The clinical trial data from the HERCULES study (n=145 patients) provides robust evidence for the plasma exchange approach combined with immunosuppressive therapy. 4 Retrospective multicenter studies (n=52 patients, n=20 patients) consistently demonstrate 75-77% overall response rates when plasma is used appropriately. 2, 3