Author Information
Chouhan T*, Tiwari N**, Chaudhari HK***.
(* Junior Resident, ** Assistant Professor, *** Associate Professor. Department of Obstetrics and Gynecology, Seth G S Medical College and KEM Hospital, Mumbai, India.)
Abstract
Glanzmann`s thrombasthenia is an autosomal recessive bleeding disorder where there is excessive bleeding inspite of normal platelet count due to platelet function defect. Here the defect lies in the human glycoprotein (Gp/gp) IIb/IIIa receptors present on the surface of platelets responsible for platelet aggregation. Patients usually present with menorrhagia, epistaxis, gum bleeding. Haematuria and GI bleeding occurs rarely. It is specially important in pregnancy as it can result in postpartum hemorrhage. We are reporting a case of Glanzmann’s thrombasthenia in pregnancy where the patient, who was a known case of Glanzmann thrombasthenia was managed successfully, and post-partum hemorrhage was prevented .
Introduction
Glanzmann thrombasthenia is a platelet function defect where there is prolonged bleeding time due to defective platelet aggregation.[1] Since it is an autosomal recessive disorder it is transmitted only when mutation is present in both the parents. The defect is in the genes that code for the glycoprotein Gp IIbIIIa receptors present on the surface of platelets responsible for platelet aggregation.
Presenting features includes easy bruising, epistaxis, bleeding from gums, menorrhagia, postpartum hemorrhage, abnormal bleeding following surgery, hematuria, hematemesis, gastrointestinal bleed or genitourinary bleed.[2] This condition is more problematic in women due to bleeding during menstruation and childbirth.
Case Report
A 30 year old primigravida, a known case of Glanzmann thrombasthenia, 29 weeks of gestation presented in the emergency with complaints of spotting per vagina and with a ultrasound (USG) scan showing a placenta previa. She was admitted. Placenta previa was excluded by a repeat USG. Hematologist was consulted for Glanzmann thrombasthenia. She was diagnosed as a case of Glanzmann thrombasthenia at menarche when he was 13 years old as she had severe menorrhagia. Flow cytometry was used to diagnose the condition. She gave history of repeated platelet transfusions since then for menorrhagia. She also had complaints of 4 – 5 episodes of haematuria. She was on cyclical estrogen progesterone combined pills (Ovral G). She consulted a hematologist and a gynecologist before conception. Hematologist advised to keep platelets ready for her and to give her NovoSeven® [recombinant human coagulation Factor VIIa (rFVIIa)] 30 mcg/kg injection prior to delivery. She was regularly cared for by the hematologist and obstetrician during this pregnancy as an outdoor case.
Chouhan T*, Tiwari N**, Chaudhari HK***.
(* Junior Resident, ** Assistant Professor, *** Associate Professor. Department of Obstetrics and Gynecology, Seth G S Medical College and KEM Hospital, Mumbai, India.)
Abstract
Glanzmann`s thrombasthenia is an autosomal recessive bleeding disorder where there is excessive bleeding inspite of normal platelet count due to platelet function defect. Here the defect lies in the human glycoprotein (Gp/gp) IIb/IIIa receptors present on the surface of platelets responsible for platelet aggregation. Patients usually present with menorrhagia, epistaxis, gum bleeding. Haematuria and GI bleeding occurs rarely. It is specially important in pregnancy as it can result in postpartum hemorrhage. We are reporting a case of Glanzmann’s thrombasthenia in pregnancy where the patient, who was a known case of Glanzmann thrombasthenia was managed successfully, and post-partum hemorrhage was prevented .
Introduction
Glanzmann thrombasthenia is a platelet function defect where there is prolonged bleeding time due to defective platelet aggregation.[1] Since it is an autosomal recessive disorder it is transmitted only when mutation is present in both the parents. The defect is in the genes that code for the glycoprotein Gp IIbIIIa receptors present on the surface of platelets responsible for platelet aggregation.
Presenting features includes easy bruising, epistaxis, bleeding from gums, menorrhagia, postpartum hemorrhage, abnormal bleeding following surgery, hematuria, hematemesis, gastrointestinal bleed or genitourinary bleed.[2] This condition is more problematic in women due to bleeding during menstruation and childbirth.
Case Report
A 30 year old primigravida, a known case of Glanzmann thrombasthenia, 29 weeks of gestation presented in the emergency with complaints of spotting per vagina and with a ultrasound (USG) scan showing a placenta previa. She was admitted. Placenta previa was excluded by a repeat USG. Hematologist was consulted for Glanzmann thrombasthenia. She was diagnosed as a case of Glanzmann thrombasthenia at menarche when he was 13 years old as she had severe menorrhagia. Flow cytometry was used to diagnose the condition. She gave history of repeated platelet transfusions since then for menorrhagia. She also had complaints of 4 – 5 episodes of haematuria. She was on cyclical estrogen progesterone combined pills (Ovral G). She consulted a hematologist and a gynecologist before conception. Hematologist advised to keep platelets ready for her and to give her NovoSeven® [recombinant human coagulation Factor VIIa (rFVIIa)] 30 mcg/kg injection prior to delivery. She was regularly cared for by the hematologist and obstetrician during this pregnancy as an outdoor case.
She was admitted at 36.3 weeks of pregnancy. USG showed gross hydrocephalus in the baby with dilatation of the 3rd, 4th and the lateral ventricle with blood clots and internal echos within the ventricles. There was blood clot in retro cerebellar region also. Poor prognosis was explained by pediatric surgeons and evaluation of the mother for mutation was advised. Platelet count of newborn was also advised. She went into spontaneous labor. All investigations were sent hemoglobin was 13.1 gm %, platelet count was1.7 lacs/ ml with normal coagulation profile. Cephalocentesis was advised for the baby in as the biparietal diameter was 11 cms. Pre-procedure 1 unit of SDP (single donor platelet) was transfused. Cephalocentesis was done were 190 ml of cerebrospinal fluid (CSF) was drained for gross hydrocephalus. She progressed normally in labor. Before delivery 4 injections of Novoseven 4 mcg was given and 6 units of RDP (random donor platelets) were transfused. She had assisted breech delivery. Baby was fresh still birth. Post-delivery vaginal pack was kept in situ to control bleeding from a cervical laceration after suturing it. A 20 IU of Pitocin drip was given and per rectally 800 mcg of misoprostol was kept. One unit of SDP (single donor platelet ) was transfused post-delivery after 12 hours followed by 6 units of RDP (random donor platelet) the next day and another SDP on day 3. Vaginal pack was removed after 6 hours. She was stable and did not have excessive bleeding post-delivery. She was discharged after hematology opinion. Contraceptive counseling was done.
Discussion
Glanzmann thrombasthenia is an autosomal recessive condition which does not manifest in heterozygous carrier states. It is estimated that one in 1,000,000 individuals have Glanzmann thrombasthenia with slight predominance in woman.[3] Fertility is not affected in case of Glanzmann thrombasthenia. There is an increased risk of post-partum hemorrhage. New born thrombocytopenia is occasionally severe but always transitory. There is problem in platelet aggregation due to defect in glycoprotein IIbIIIc resulting in prolonged bleeding time and defective clot retraction. Patients will have normal platelet count and coagulation profile but with increased bleeding time. Platelet aggregation in presence of collagen and ADP will be impaired as this requires fibrinogen whereas the one with ristocin will be normal.[4]
Glanzmann thrombasthenia is further divided into type I where < 5 % receptors (GpIIbIIIa) are present and aggregation of platelets will be absent, type II where 5-20% receptors are present and function of platelets is impaired but not absent and type III where receptors are present but function is defective. Most common presentation in non pregnant women is menorrhagia which is controlled initially with tranexamic acid and oral contraceptive pills. Injection testosterone or injection leuprolide is helpful in severe cases but specific management includes platelet transfusion. Obstetric patients have high risk of developing post-partum hemorrhage. Definitive diagnosis is based on flow cytometry where CD 41 and CD 61 receptors for GpIIb and GpIIIa and fibrinogen receptors are absent.[4] For preventing post-partum hemorrhage adequate platelets should be kept ready before delivery. Most patients will have history of multiple platelet transfusion which result in development of antibodies and risk of alloimmunization increases with successive pregnancies. Repeated platelet transfusion is required in patients to control bleeding. Use of antiplatelet drugs like aspirin and other NSAIDs are contraindicated in such patients. Other control measures include use of oral contraceptives to control menorrhagia and use of Novoseven. This activated factor Novoseven is reserved for people who have already developed antibodies after several platelet transfusions.[2]
Novoseven which is an activated factor is helpful in this condition.[5] Novoseven was initially used in management of hemophilia but its role has increased in management of Glanzmann thrombasthenia. It is specially useful in this case as due to platelet transfusion these patients have antibodies against platelets and therefore a directly acting activated factor 7 is more effective. Intramuscular injection should be avoided. Patients with mutations detected should be adequately counseled about risk of transmission to the fetus. Pregnant patients develop bleeding post-partum and even during puerperium which can be controlled by use of uterotonics followed by platelet transfusion.These patients have increased risk of maternal and fetal bleeding and high chances of neonatal deaths.[6]
Conclusion
Prognosis of Glanzmann thrombasthenia is good when proper supportive care is given. Post-partum bleeding can be serious and requires timely intervention. This case highlights the need of timely replacement of platelets and proper measures to prevent post-partum hemorrhage for managing a patient with Glanzmann thrombasthenia.
References
- Pittman MA, Graham JB Glanzman’s Thrombopathy: an autosomal recessive trait in one family. Am J Med Sci. 1964;247:293-303.
- Poon M-C. Clinical use of recombinant human activated factor VII (rFVIIa) in the prevention and treatment of bleeding episodes in patients with Glanzmann’s thrombasthenia. Vasc Health Risk Manag. 2007; 3(5): 655–664.
- Sundqvist S-B, Nilsson IM, Svanberg L, Cronberg S. Pregnancy and parturition in a patient with severe Glanzmann’s thrombasthenia. Scand J Haematol. 1981;27(3):159-64.
- Sharp WJ, Khanduri UD, Christie BS. Rapid heterozygote detection in Glanzmann’s thrombasthenia. Br J Haematol 1998;101(1): 66 –9
- Fernandes G M, de Melo RM, Plens G, Pontes EM, Silva MM, da Rocha JC. Surgical and clinical management of a patient with Glanzmann thrombasthenia: a case report. Quintessence Int. 2004;35(8):617-20.
- Balci YI, Karabulut A, Sibel Kabukcu S, Sari I, Keskin A. Intensive Menstrual Bleeding Successfully Treated With Recombinant Factor VIIa in Glanzmann Thrombasthenia. Clin Appl Thrombo Hemost. 2011;17(4):320:2.
- Fiore M, Nurden AT, Nurden P, Seligsohn U. Clinical utility gene card for: Glanzmann thrombasthenia. Eur J Hum Genet. 2012;20(10):1102.
Chouhan T, Tiwari N, Chaudhari HK. Management Of a Rare Case Of Glanzmann`s Thrombesthenia In Pregnancy. JPGO 2018. Volume 5 No.10. Available from: http://www.jpgo.org/2018/10/management-of-rare-case-of-glanzmanns.html