Glanzmann's thrombasthenia (GT) is a rare genetic platelet disorder in which the platelet membrane glycoprotein IIb/IIIa complex is deficient or dysfunctional, leading to defective platelet aggregation and subsequent bleeding. It is inherited in an autosomal recessive pattern1 and clinically apparent only in homozygous recessive patients. It is most prevalent in four populations worldwide that have a greater level of consanguinity, namely French gypsies, Iraqi Jews, Jordanian Arabs and Indians. There is a greater preponderance in females2 and common clinical presentations include purpura, petechial haemorrhages, gingival bleeding, epistaxis and, in females, menorrhagia, which worsens during menarche. Less common presentations include haemarthroses, haematuria, gastrointestinal bleeding2 and haemorrhagic ovarian cysts. Luteal haemorrhage is very rare in GT and described in only two cases in the literature. The patient described below had a history of menorrhagia and presented with recurrent episodes of acute abdomen, marking pelvic haemorrhage.
Miss MK, a 22-year-old local and unmarried woman, was admitted to the gynaecology department at Latifa Hospital on 24 March 2012 complaining of lower abdominal pain and nausea, which she had been suffering for 2 days. She had been referred from another hospital for further management as ultrasonography had revealed a ruptured right ovarian cyst with haematoma formation in the pelvis. Latifa Hospital is a tertiary-level care hospital for obstetrics and gynaecology for the northern Emirates; thus, the patient was transferred there.
Miss MK was diagnosed with Glanzmann's disease during childhood and had been having regular appointments with a haematologist in another emirate. She had experienced an episode of ruptured ovarian cyst 1 year previously, at which time she was diagnosed as having endometriosis and was treated conservatively and prescribed the combined hormone pills for 4 months. At the time of admittance to Latifa Hospital, she was on tranexamic acid tablets during her periods. She experienced menarche at 17 years of age and her cycles had always been irregular with a heavy flow lasting 7 days. Her last menstrual period was 11 days previously. Her parents were first cousins and she had two sisters and one brother also suffering from GT.
On examination, she was pale but did not show icterus and had normal vital signs. Her chest was clear but there was tenderness in the suprapubic region and left iliac fossa with guarding but no rigidity. There was no bleeding per vaginam and laboratory investigations showed haemoglobin levels of 6.9 g% (which had dropped from 8.7 g% in the referring hospital), her platelet count was 122 000/mm3 and a coagulation study was normal. Bleeding time (the time taken for a superficial cut to stop bleeding) was prolonged to 15 minutes (beyond the normal range of 2–2.9 minutes), a urine pregnancy test was negative and a urine culture showed no growth. The patient's glucose levels and right and left fallopian tubes were normal. Ultrasonography of the abdomen and pelvis showed a normal-sized uterus but a large right adnexal heterogeneous mass of more than 10 cm in diameter, extending to the pouch of Douglas and left adnexa, with no vascularity on colour Doppler (suggestive of blood clots) (Figure 1). There was mild to moderate fluid collection in the right paracolic gutter, Morrison's pouch (Figure 2) and splenorenal pouch, and the vascularity of both ovaries were preserved on colour Doppler (Figures 3 and 4). The right ovary had a cyst of 2 × 2 cm and left ovary had a cyst of 3 × 3 cm.
In view of the patient's previous history and clinical condition, conservative management was planned and the case was discussed with a consultant haematologist, who advised that surgery and platelet transfusion should be avoided to prevent formation of antiplatelet antibodies. Four units of packed red blood cells (RBCs) and intravenous tranexamic acid 1 g tid were administered. Abdominal pain improved on the second day after admission but then menstruation began. Oral tranexamic acid 500 mg tid and the combined oestrogen + progesterone pill was prescribed. She was stable during her stay in hospital and her haemoglobin levels improved to 11.2 g% after 4 days, at which time she was discharged. A review with a haematologist was arranged for 2 weeks later and ultrasonography repeated at 2 weeks showed no change in the size of the haematoma.
The patient was reviewed in the gynaecology clinic at Latifa Hospital after 6 weeks and she was clinically stable. Ultrasonography showed a reduction in the size of the haematoma, which was 8 × 6 cm. She was advised to continue taking the combined hormonal pill.
Four months later, she was readmitted to Latifa Hospital with abdominal pain and a heavy period. Her haemoglobin level was 7.6 g% but her platelet count and coagulation studies were normal. Serum CA-125 was 125.8 international units (U)/ml. Ultrasonography showed a heterogeneous right adnexal mass of 8 × 6 cm (Figure 5) with ascites overlying the pelvis and abdomen. The patient improved following a blood transfusion and regular tranexamic acid. Gonadotropin releasing hormone (GnRH) injections were advised cyclically for 3 months and a follow-up appointment for a repeat ultrasound was booked in the endometriosis clinic.
The management of patients with GT is challenging and requires multidisciplinary input. The severity of bleeding varies from mild to serious, life-threatening, haemorrhage requiring aggressive and invasive treatment.3 Patients with GT typically present with mucocutaneous bleeding at birth or early in infancy. Laboratory criteria for diagnosis of this disorder include normal platelet count and morphology, normal plasma coagulation studies, prolonged bleeding times, absent or severely diminished platelet aggregation in response to adenosine diphosphate and other agonists and normal agglutination with ristocetin.3 Patients with severe glycoprotein IIb/IIIa deficiency (< 5% of the normal level) and absent clot retraction are classified as having type I GT and those with moderate deficiency (10–20% of the normal level) and delayed clot retraction are classified as having type II GT. Types with defective receptor function are called variants.3 The severity of bleeding is independent of type of defect and carriers of GT or heterozygotes have normal haemostatic function.
In patients with GT who present with bleeding, medical measures include antifibrinolytic agents (such as tranexamic acid) and blood and blood product transfusions to correct anaemia. When these measures fail, platelet transfusions are considered.4 Repeated platelet transfusions can lead to formation of GP IIb/IIIa antibodies and/or human leucocyte antigen (HLA) immunization and development of platelet refractoriness. Such cases benefit from recombinant factor VIIa (Novoseven)™ (Novo Nordisk, Küsnacht, Switzerland) therapy, which is currently approved for use in GT in Europe and Saudi Arabia.5 Cases with documented alloimmunization may benefit from plasmapheresis, which leads to transient reduction of antibody titre and control of acute severe bleeding.8 Menorrhagia can be controlled by high-dose progestins followed by the combined oral contraceptive pill for maintenance. Bone marrow transplant from a HLA-identical sibling donor may be considered in selected cases of GT with persistent life-threatening haemorrhage,1 but only after careful assessment of the risk–benefit ratio of such a procedure.
In the case reported by Al-Sahhaf and Al-Zahrani,5 a pelvic haematoma was measured at 6 × 9 cm and was managed by repeated platelet and packed RBC transfusion, intravenous tranexamic acid and ultrasonography guided intra-abdominal aspiration. Bayukasik et al.6 reported a case in 2012 of a large abdominal pelvic haematoma as a result of ovulation in a patient with GT that could be treated only by surgery and intra-abdominal tranexamic acid. Our patient presented with recurrent pelvic haematoma with acute abdomen but could be managed by tranexamic acid and packed RBC transfusion alone.
Endometriosis is more common in females with GT. Alatas et al.7 reported two cases of histopathologically confirmed endometriosis in two sisters aged 24 and 28 years, who had been previously diagnosed with GT. Our case had also been clinically diagnosed in another hospital as having endometriosis.
Pregnancy and delivery is a potentially dangerous time for women with GT,3 when platelet transfusion, blood transfusion and Novoseven therapy may be required. Patients with GT should be vaccinated against hepatitis and medications that affect platelet function should be avoided.
Glanzmann's thrombasthenia is a rare genetic disorder of platelet aggregation characterized by life-long bleeding tendency prevalent in the offspring of consanguineous marriages. Spontaneous bleeding is uncommon but post-traumatic, postoperative haemorrhage can be serious.8 In women of reproductive age, physiological events such as ovulation and corpus luteum cyst rupture can cause extensive intra-abdominal haemorrhage. The management of GT is challenging but successful with a multimodality approach. It is essential for all clinicians to be aware of such rare coagulation disorders when women present with acute abdomen and to avoid surgical intervention before considering medical measures.