TREATMENT OF SEVERE FETOMATERNAL ALLOIMMUNE THROMBOCYTOPENIA WITH COMPATIBLE FROZEN–THAWED PLATELET CONCENTRATES
We read with interest the recently published paper (Ranasinghe et al, 2001) on the provision of platelet support for fetuses and neonates affected by severe fetomaternal alloimmune thrombocytopenia (FMAIT). In this situation, there is a high risk of potentially life-threatening bleeding while the number of thrombocytes remains below 20–30 × 109/l, and the most rapid and effective treatment is immediate transfusion of compatible platelets (Letsky & Greaves, 1996). The antibodies involved are anti-human platelet antigen (HPA)-1-a in 80–90% of cases and anti-HPA-5-b in 5–15% of cases, with other platelet antibodies rarely involved (Letsky & Greaves, 1996). Ranasinghe et al (2001) screened over 60 000 blood donors to obtain 45 HPA-1-a-negative donors suitable for plateletpheresis and available if fetal or neonatal platelet transfusion was required.
We would like to report another approach tested by our blood centre, which has developed a protocol to maintain a permanent stock of HPA-1-a-negative platelet concentrates (PC). Group O plateletpheresis blood donors are routinely HPA phenotyped by our Platelet Immunology Laboratory to provide a panel for platelet antibody screening. We therefore established a cohort of platelet blood donors phenotyped for the HPA-1, 3 and 5 systems and for the CD36 molecule. For these donors, HPA phenotyping is performed twice and we screen for antibody to HPA antigen in HPA-1-a-negative donors using the Platelet Suspension Indirect Immunofluorescence Test (PSIIFT) and the Monoclonal Antibody-specific Immobilization of Platelet Antigen (MAIPA) test. The 363 plateletpheresis blood donors phenotyped for HPA systems and attending our blood centre include 10 currently active HPA-1-a/HPA-5-b-negative donors, without platelet antibody. These donors can give platelets up to three times a year for men and twice a year for women. The adult HPA-1-a-/HPA-5-b-negative PC obtained (one adult PC contains a mean of 4–7 × 1011 platelets) are divided into two or three paediatric PC, which are then frozen in dimethylsulphoxide (DMSO) for cryoprotection (final concentration 5%) within 24 h, preferably at −196°C in liquid nitrogen, but occasionally at −80°C in a freezer (Barnard et al, 1999). Under French legislation, PC treated in this way may be stored for up to 3 years. At each platelet donation, blood donors are systematically subjected to the following mandatory tests: blood groups ABO Rhesus and Kell, tests for antibodies against erythrocyte antigens other than ABO, high titres of anti-A and/or anti-B, infectious markers such as alanine aminotransferase (ALT), hepatitis B virus (HBV) surface antigen (HBsAg), HBV antibody (HBcAb), antibodies against hepatitis C virus (HCV), human immunodeficiency virus (HIV) 1/2, Human T-lymphotropic virus (HTLV) I/II and the agent of syphilis, HCV and HIV antigens using polymerase chain reaction (PCR) screening. Tests for cytomegalovirus (CMV) antibody are also performed if previous test results were negative. PC are accredited only if the clinical assessment has been successfully validated by the blood donor and if mandatory tests present no abnormalities.
In cases of severe FMAIT requiring transfusion, accredited frozen PC are thawed and washed. This operation takes no longer than 90 min. The paediatric unit is then infused into the thrombocytopenic neonate in a volume of 20 ml/kg, generally leading to a significant increase in platelet counts (Table I).
| Neonate | Clinical manifestations | Platelet count before transfusion of compatible PC ( × 109/l) | Platelet count 24 h after transfusion ( × 109/l) | Associated treatment | Progression |
|---|---|---|---|---|---|
| 1 | Petechia and haematoma at h 9 of life | 9 | 230 | IVIg† | No recurrence of thrombocytopenia |
| 2 | Petechia and haematoma at h 12 of life | 12 | 350 | IVIg | No recurrence of thrombocytopenia |
| 3 | Thrombocytopenia discovered by chance on d 3 of life | 7 | 235 | IVIg | No recurrence of thrombocytopenia |
| 4 | Petechia at birth | 12 | 45 | IVIg | No recurrence of thrombocytopenia |
| 5 | Digestive haemorrhage and petechia at h 36 of life | 8 | 85 | IVIg | Progressive decrease in platelet count to 26× 109/l on d 7 – 2nd transfusion of PC on d 8 |
| 6 | Petechia and ecchymosis at birth | 5 | 100 | None | No recurrence of thrombocytopenia |
| 7 | Petechia and ecchymosis at h 24 of life | 23 | 250 | IVIg corticosteroids | No recurrence of thrombocytopenia |
| 8 | Petechia and haematoma at venepuncture sites | 13 | 168 | None | No recurrence of thrombocytopenia |
| 9 | Purpura rash | 22 | 112 | None | No recurrence of thrombocytopenia |
| 10 | None (history of previous FMAIT, platelets counted systematically) | 15 | 324 | None | No recurrence of thrombocytopenia |
- * A paediatric dose contains 1·5–2 × 1011platelets and is infused in a volume of 20 ml/kg.
- † IVIg (intravenous immunoglobulin) was administered at a dose of 1 g/kg/d for 1 or 2 d.
- PC, platelet concentrate; h, hour; d, day; FMAIT, fetomaternal alloimmune thrombocytopenia. This table reports the 10 most recent cases of FMAIT due to HPA-1-a antibody requiring the infusion of compatible platelets. The time between diagnosis of thrombocytopenia and PC infusion did not exceed 12 h.
In our experience, this approach is the most rapid and safest way to provide HPA-compatible PC, particularly because blood donors, even if available when called, may be disqualified from blood donation on clinical grounds or as a result of abnormal results in mandatory biological tests. Furthermore, for each blood donation, there is a waiting period of 24–48 h before the results of the tests required for certification of the PC become available. If the approach described here is used, accredited HPA-phenotyped PC are always available within a reasonable time period.
