A 29 year old female presented to the Casualty Department feeling generally unwell. At 28 weeks gestation she was hypertensive with proteinuria. She had with her an Advanced Health Care Directive stating that no transfusions of whole blood, red cells, white cells, platelets or plasma be administered to her. She was admitted with a presumptive diagnosis of pre-eclampsia.
A full blood count and coagulation studies were performed with the following results:
|Hb 103 g/L||WBC 10.5 x 109/L||Platelets 24 x 109/L|
|PT 15.8||sec INR 1.2||APPT 27.4 sec|
|Fibrinogen 1.4 g/L||D- DIMER LIA >20.00 ug/ml|
She was severely thrombocytopenic with disseminated intravascular coagulation (DIC). The blood film and differential count showed the presence of 15% blast cells and 55% abnormal promyelocytes. A diagnosis of acute promyelocytic leukaemia (APL) was made. A bone marrow aspiration was performed. The differential count on the bone marrow showed the presence of 86% abnormal promyelocytes. Cytogenetics showed a t(15;17). FISH confirmed a PML/RARA fusion. Immunophenotyping was as follows:
CD45+, HLA-DR-, CD11b-, CD13+, CD15-, CD33+, CD34-, CD64+, CD117+, CD2+, CD22+ and MPO+
The above patient was transferred to a ward under joint obstetric and haematology care. A number of issues were before this medical team. They were presented with a patient with APL, DIC and severe thrombocytopenia. She was 28 weeks pregnant with pre-eclampsia and from deeply-held conviction, refused blood product support. Therefore performing a caesarean section was not safe. She was given steroids for fetal lung maturity as well as all trans retinoic acid (ATRA), the drug of choice for the treatment of APL.
Over the next few days the white cell count steadily rose as did the urea, creatinine and liver function tests. Her hypertension was difficult to control. Labour was induced with failure to progress. On the ninth day after admission, a stillborn fetus was delivered vaginally. There was minimal blood loss. It is thought that the stillborn infant was directly related to the acute renal failure in the mother.
By day ten the patient started to deteriorate. The white cell count had increased to 61 x 109/L, the Hb was 48 g/L and platelet count 17 x 109/L. Her renal function had deteriorated. The blood urea was 24.0 mmol/L and creatinine 282 mmol/L. The liver function became acutely deranged – GGT 59 U/L, AST 80 U/L and ALT 369 U/L.
She was admitted to intensive care where she was intubated. Her neurological function deteriorated. She was now hemiplegic. By day twelve there was further deterioration in her neurological function. On day thirteen treatment was withdrawn.
There are two types of APL. The hypergranular or typical type characterised by abnormal promyelocytes whose cytoplasm is densely packed with granules and Auer rods and the hypogranular or microgranular type whose cytoplasm shows a paucity or absence of granules and occasional Auer rods. The granules in these abnormal promyelocytes contain procoagulant mediators which, when released into the circulation, cause a life-threatening coagulopathy or DIC. The dilemma with the above patient was her severe thrombocytopenia, DIC and her refusal to accept blood products. Current therapy of ATRA combined with chemotherapy results in 70 to 80% patient survival and disease-free outcome after five years.
The initial visit by this patient to the hospital was to surrender an Advanced Health Care Directive stating that she would not accept a transfusion of red cells, white cells or platelets. As an adult she is able to make this decision. In the case of a child, a court order would ensure that the child be treated appropriately.