Author
Information
Pawde
Anuya*, Patil Devendra**, Khadkikar
Rashmi***, Chauhan AR
(* Senior
Registrar, ** Second Year Resident, *** Assistant Professor, **** Additional
Professor. Department of Obstetrics and Gynecology, Seth
G.S. Medical
College and K.E.M
Hospital , Mumbai , India
Abstract
Hereditary
bleeding disorders are an important cause of puberty menorrhagia and the
consequences can be life threatening. A twelve year old girl, known case of
Factor V and VIII deficiency, presented to a tertiary care centre at menarche
with menorrhagia. She was successfully managed with transfusions of
cryoprecipitate, fresh frozen plasma (FFP) and Factor VIII concentrate along
with oral progesterone. She is now on oral contraceptive pills. This case is
presented as combined factor deficiency is a rarity. Early diagnosis,
consultation with hematologist and appropriate treatment are essential.
Introduction
Puberty menorrhagia is defined as bleeding of more than 80 ml/cycle or for more than 7 days. Most common cause of puberty menorrhagia is immature hypothalamo-pituitary-ovarian axis. Other causes include hereditary bleeding disorders, hypothyroidism, and anovulatory cycles due to polycystic ovarian disease. Hemophilia, though not very common, is an important cause for puberty menorrhagia and can be life threatening. It usually presents with excess bleeding at menarche with mid-cycle abdominal pain. History of repeated excess bleeding from gums or wounds along with family history of similar complaints may be corroborative. [1,2]
Case
Report
Miss RRG
12 year old girl presented with history of attainment of menarche 3 days ago
with excessive vaginal bleeding, with use of 6-7 large pads per day. Bleeding
was not associated with pain in abdomen or any other complaints. She was a
diagnosed case of Factor V and Factor VIII deficiency since the last 8 years,
and gave history of multiple blood transfusions, fresh frozen plasma and
cryoprecipitate transfusions in the past. There was no history suggestive of
thyroid disorder or tuberculosis. Family history was significant; her younger
brother aged 8 was diagnosed in infancy as a case of Factor VIII deficiency
after multiple bleeding episodes and her father, though asymptomatic, is also
Factor VIII deficient.
On
examination the patient was stable, with mild pallor. There was no evidence of
petechiae or bruising. Thyroid, breast and systemic examinations were
unremarkable. Abdomen was soft and non-tender. On local examination bleeding
with clots was seen. Per rectal examination revealed small uterus.
On
investigations, hemoglobin was 8.8 g%, platelet count was normal. Significant
abnormality was seen in coagulation profile with abnormal prothrombin time (PT
19.4 against control of 8.9), activated partial thomboplastin time (APTT 87.1
vs 28.0 control) and International Normalised Ratio (INR) of 2.18. Ultrasonography revealed normal uterus and
ovaries.
In
consultation with hematologist, patient was transfused 3 units of
cryoprecipitate and 2 units of fresh frozen plasma daily along with oral
tranexamic acid thrice daily. However, despite this, the bleeding continued in
the same amount for next 3 days. Hence oral medroxyprogesterone acetate was
added in the dose of 5mg thrice daily. Oral iron and folic acid supplementation
was given for correction of anemia. Bleeding did not respond completely to
treatment, hence Factor VIII concentrate in the dose of 50IU/kg was transfused;
bleeding stopped on day 8 of treatment. Subsequently, she was started on oral
contraceptive pills, was counseled and discharged.
Discussion
Bleeding
disorders should be suspected in patients with puberty menorrhagia with history
of repeated gum bleeding, delayed wound healing, easy bruising, epistaxis,
bleeding from tooth extraction, repeated blood transfusions and family history.[3]
Commonly seen disorders are hemophilia A and B (deficiency of factor VIII
and IX respectively), von Willebrand disease, factor V deficiency, Glanzmann’s
thrombasthenia, and idiopathic thrombocytopenia. Though combined deficiencies
as seen in our case are known to occur, they are rare and have severe
consequences.
Combined
factor V and VIII deficiency is a rare autosomal recessive disorder with
incidence of 1 in 1,000,000 cases, caused by a single gene defect in chromosome
18.[3,4] In extremely rare cases (1 in 10 billion) factor V and
factor VIII could be inherited separately instead of a single gene defect.[3]
Treatment
modalities used to control bleeding are tranexamic acid, progesterone alone or
oral contraceptive pills, though often bleeding may not respond to these drugs
alone. Factor V deficiency can only be treated by FFP in the dose of
15-20ml/kg. FFP is also rich in factor VIII; however FFP alone may be insufficient
to treat Factor VIII deficiency and additional treatment with factor VIII
concentrate may be required. This concentrate may be plasma derived or
recombinant factor VIII, in the dose of 20-50IU/kg as per requirement. [5]
Other drug that has been used for factor VIII deficiency is desmopressin.
Hereditary
bleeding disorders should be suspected in all cases of puberty menorrhagia.
Detailed personal and family history may guide to the diagnosis and appropriate
treatment may prevent life threatening consequences.
References
1. Bevan JA. Bleeding disorders: A common cause of menorrhagia in
adolescents. J Pediatr.2001 Jun; 138(6):856-61
2.
Mikhail S, Varadarajan R, Kouides P. The
prevalence of haemostasis in adolescents with menorrhagia referred to a
haemophilia treatment centre. Hemophilia
2007; 13: 627-632.
3.
Kenneth Kaushansky. Inherited deficiencies of
coagulation factor II, V, VIII, X, XI, XIII, combined deficiency of Factor V
and VIII and of Vitamin K- dependant factors. Kenneth Kaushansky, Ernest Beutler, Marshall A
Lichtman. Williams Hematology. 8th edition. China
4.
Spreafico M, Peyvani F. Combined FV and FVIII
deficiency. Hemophilia 2008;14:1201-1208.
5.
Fogarty PF, Kessler CM. Hemophilia A and B. In
Kitchens C, Kessler C, Konkle B, editors. Consultative Hemostasis and
Thrombosis; 3rd ed. Elsevier. 2013; pp 50-53.
Citation
Pawde
A, Patil D, Khadkikar R,
Chauhan AR.