Glanzmann Thrombasthenia in Pregnancy

Dear Editor,

A 28-year-old lady with 18⁺⁴ weeks pregnancy was referred to medicine and hematology when her obstetrician elicited a history of mucocutaneous bleeding, initially of uncertain significance. Although insistent that she was “fine” with only “heavy periods,” the clinician’s suspicions were aroused when the patient volunteered that she had once required hospitalization following severe menorrhagia and received 2 units of packed red cells due to blood loss 3 years ago. On detailed probing, it also emerged that excessive bleeding was, in fact, present since early childhood and although very intermittent, tended to be severe in nature. As a 4-year-old, she had been hospitalized and transfused blood following uncontrolled bleeding from a tongue injury received during playtime. At that time, she had been investigated, but old papers were unavailable and her parents had been reassured that she would most likely grow out of the problem. There was no history of bleeding from the umbilical cord stump, no history of consanguinity or any similar illness in her family, and no history of bleeding from a site other than skin, oral mucosa, or menorrhagia.

Despite being currently complaint-free and the screening laboratory studies (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and thrombin time, Table 1 ) returning to normal, her care providers decided to proceed with further testing.

Table 1.

Routine Hematological and Screening Coagulation Parameters

Parameter	Results	Reference Range
Hemoglobin (g/dL)	16.8	12-16
Total WBC Count (per μL)	10,800	4,000-10,000
Platelet Count (per μL)	1,44,000	1,50,000-4,00,000
Mean Platelet Volume (fl)	8.8	7.0-10.5
Prothrombin time (s)	12.6	10.0-13.2
Activated partial thromboplastin time (s)	32.4	25.1-36.7
Thrombin time	21.3	19.2-23.8
Fibrinogen level (g/L)	4.207	2.0-4.0

Her von Willebrand antigen level was normal for blood group. Clot retraction at 1 hour was deficient and yielded a ratio of expressed serum volume to total volume of 20% (expected normal value >40%). ¹ Light transmission platelet aggregometry (Chronolog Corp, Pennsylvania, USA) revealed virtually absent platelet aggregation responses to arachidonic acid (0.75 mmol/L), collagen (2 μg/mL), adenosine diphosphate (10 μmol/L), and epinephrine (10 μmol/L). Responses to ristocetin (high dose, 1.25 mg/mL and low dose, 0.25 mg/mL) were normal (Figure 1A, B, and C and Table 2 ). The diagnosis of Glanzmann thrombasthenia (GT), type 2 was confirmed when flow cytometric studies showed reduced surface expression of gpIIb (CD41) on her platelets.

Figure 1.

A, Markedly reduced aggregation with arachidonic acid and collagen. B, Markedly reduced aggregation with adenosine diphosphate and adrenaline. C, Normal aggregation responses with high- and low-dose ristocetin.

Table 2.

Light Transmission Platelet Aggregometry Results

Agonist	% Aggregation		Normal Range of Laboratory	Interpretation of Response
	Test	Control
ADP 10 μmol/L	10	72	71%-88%	Deficient
Epinephrine 10 μmol/L	00	67	71%-90%	Deficient
Collagen 2 μg/mL	01	75	70%-94%	Deficient
Arachidonic acid 0.75 mmol/L	03	81	72%-99%	Deficient
Ristocetin 1.25 mg/mL	86	87	87%-102%	Normal
Ristocetin 0.25 mg/mL	01	02	0%-4%	Normal

She had an uneventful pregnancy under heightened medical watchfulness. She was already immunized for hepatitis B and her antibody titers were ascertained. Delivery was at term and through an elective lower segment caesarean section (LSCS). One unit of the single donor platelets kept ready was required to effectively control postoperative oozing, at a near-normal platelet count. The neonate had a normal platelet count. Both the mother and the baby were complaint-free at last follow-up, 3 months post-LSCS.

Although rare overall, GT is the commonest inherited platelet function defect found in Indian women with menorrhagia. ² Patients with this autosomal recessive disorder, resulting from a deficiency or defect in the platelet surface glycoprotein IIb/IIIa (integrin αIIbβ3) or its regulatory elements usually display a severe bleeding phenotype. ³ Diagnosis is based on deficient platelet aggregometric responses to multiple agents, with normal agglutination in response to ristocetin. ³ Similar patterns may be obtained in afibrinogenemia, ⁴ but this was excluded by a normal thrombin time and fibrinogen levels in our case.

Severe bleeders, especially in India, may go undiagnosed for prolonged periods of time due to the nonavailability or nonaffordability of specialized tests. ⁵ Women may underestimate the severity of their symptoms ⁶ and the suspicion of chronic ill health too may be socially detrimental. ⁷ Physicians may be reassured by a normal coagulation screen or may be unaware of the significance of rare inherited platelet function disorders as well as of the appropriate tests to order.^8,9 This may be compounded by the lack of uniformity among laboratories in the methodologies employed for platelet function testing and their quality control. ¹⁰

Apart from adding to the published literature on successful obstetric outcomes in patients with GT, this case serves as a striking reminder of the life-saving importance of a high index of suspicion for a potential bleeding disorder in patients facing major hemostatic challenges like parturition. Timely diagnosis of inherited thrombocytopathy by an alert clinician likely averted catastrophic hemorrhage post-LSCS, a time when an accurate primary diagnosis would have been virtually impossible and platelet transfusion therapy would not have been considered. A detailed bleeding history regardless of the coagulation screen results and apparent asymptomatic state remains an excellent “diagnostic test” for bleeding disorders. ¹¹