When Transfused Platelets Backfire: Understanding Post-Transfusion Purpura

Two weeks after a massive transfusion protocol for hemorrhagic shock, one of our patients developed profound thrombocytopenia — counts dropping to single digits despite transfusions. Each additional platelet unit seemed to make things worse, not better. Within days, she developed intra-abdominal bleeding that required surgical exploration and an open abdomen.

When the post-transfusion purpura (PTP) panel came back, it revealed an alloantibody against HPA-1b — an uncommon finding, but one that instantly clarified what had happened.

What Is Post-Transfusion Purpura?

PTP is a rare, delayed transfusion reaction characterized by sudden, severe thrombocytopenia appearing 5–12 days after transfusion. The syndrome occurs most often in individuals who lack the common platelet antigen HPA-1a and have been previously sensitized, typically through pregnancy or prior transfusion.

The most common culprit antibody is anti-HPA-1a, but antibodies to other platelet antigens — including HPA-5a, HPA-4a, HPA-3a, and rarely HPA-1b — have been described.

Regardless of the specific target, the result is the same: the patient’s immune system destroys both transfused and autologous platelets, leading to precipitous thrombocytopenia and risk of life-threatening bleeding.

A Quick Detour Into HPA Genetics

The HPA-1 system is defined by two alleles:

• HPA-1a, found in roughly 75–95% of most populations.

• HPA-1b, a minor allele whose frequency ranges from 10–24% in many European and Middle Eastern groups, but is <1% in East Asian populations.

  
  

This population variation matters. In regions where HPA-1b is rare, like the US, compatible donors for patients with anti-HPA-1b can often be found locally, as most platelet units will be negative for HPA-1b. In the US, sourcing units for patients with anti-HPA-a1 is the reverse — the search for HPA-1b-positive, 1a-negative donors is extraordinarily difficult.

Diagnosing PTP

PTP should be suspected when:

• Severe thrombocytopenia develops 5–10 days post-transfusion,

• There is a paradoxical worsening of counts after platelet transfusion, and

• There is no evidence of DIC, HIT, or marrow suppression.

  
  

Diagnosis is confirmed by detecting platelet-specific alloantibodies in the patient’s serum — most commonly anti-HPA-1a. In this case, however, the antibody was anti-HPA-1b, underscoring that the immunologic mechanism is the same even when the target is rare.

Treatment: Why IVIG Works (and Platelets Usually Don’t)

The mainstay of treatment is intravenous immunoglobulin (IVIG) — typically 2 g/kg divided over 2–5 days.

• IVIG acts by saturating Fc receptors, blunting macrophage-mediated platelet destruction, and modulating the immune response.

• It leads to a platelet recovery in ~85% of reported cases, usually within several days.

  
  

Plasma exchange can be considered in refractory cases or when IVIG is unavailable, though evidence is limited.

What doesn’t work well is platelet transfusion. Even HPA-matched platelets are often rapidly destroyed in the presence of circulating antibody. Their use is generally reserved for life-threatening bleeding when IVIG has failed or is contraindicated. Reports of transient benefit exist, but consistent success is rare.

For long-term management, future RBC transfusions should be washed to remove residual platelets and platelet antigens, and HPA-compatible platelets should be considered to avoid re-exposure and further alloimmunization.

Reflection From the Bench

This case was a reminder that transfusion medicine sits at the crossroads of immunology and critical care. PTP may be rare, but when it strikes, it can upend a patient’s course and confound even seasoned teams.

The irony of PTP is striking: transfused platelets meant to heal instead trigger the destruction of every platelet in circulation. But timely recognition, serologic confirmation, and early IVIG can turn the tide — and save both platelets and lives.

When I called hematology with the antibody result today, they immediately pivoted to planning for HPA-matched support before the patient’s next surgery. That’s the value of diagnosis — not just knowing what went wrong, but knowing how to protect the patient the next time around.