A CASE REPORT OF BERNARD-SOULIER SYNDROME IN DIFFERENTIAL DIAGNOSIS OF IMMUNE THROMBOCYTOPENIC PURPURA

Lina Ahmed Wasfi, Abdul Rahman Hassan Issa, Shatha Ahmad Awad Aljuhani, Ruaa Omar Nughays, Walaa Mohammed Hafez Hassan and Tyseer Hassan Ahmed Hassan. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


ISSN: 2320-5407
Int. J. Adv. Res. 6(1), 120-130 121 The patient diagnosed as idiopathic thrombocytopenia. Received IVIG and discharged in good condition.In addition, she had multiple admissions due to the same complain petechiae and low platelet count. She received IVIG many times, and she responded as platelet count increase at least by 30.000 but after two to four weeks platelets drop again even below 10.000. There was no respond to steroids. She responded to anti-D once for four weeks. She received four doses of rituximab there was no respond until 16 weeks. Bone marrow aspiration and biopsy were done on 30/3/2015 before receiving steroids; the result was cellular normal marrow. Normal megakaryocytes content on the marrow. No pathology on the marrow to explain the thrombocytopenia.
She was diagnosed as chronic ITP with frequent admission and poor response to treatment and due to hospital logistic issues platelets aggregation and flow cytometry not done.The doctor arranged an appointment for follow-up and genetic analysis for Bernard-Soulier syndrome. The result of Molecular genetic analysis of the genes GP1BA, GP1BB, GP9 showed a presence of a homozygous deletion of 39 nucleotides in the exon 2 of GP1BA. Finally, she diagnosed as Bernard-Soulier Syndrome (BSS).

Discussion:-
Bernard-Soulier syndrome is an autosomal recessive disorder. Bernard-Soulier syndrome affects both males and females [10] .In Bernard-Soulier syndrome, thrombocytopenia is associated with morphologically abnormal large platelets and platelet dysfunction. The clinical manifestation is variable and includes purpura, epistaxis, gingival bleeding, menorrhagia, occasional gastrointestinal bleeding, hematoma, or hematuria.The diagnosis of platelet function disorders needs a detailed medical history and a series of laboratory tests.
In people with Bernard-Soulier syndrome:  The bleeding time is difficult to perform in young children.  The closure time is prolonged.  Larger platelets.  Platelets appear on the blood film.  There are usually fewer platelets than normal.  Platelets do not clump together normally in the presence of ristocetin.  GPIb/IX/V is not detectable by flow cytometry [10].
Reasons to suspect hereditary thrombocytopenia [11] (See Table 1) Classification schemes for hereditary thrombocytopenia [11] (See Table 2) On (Table 3 and 4) showed Mutations Identified and some diseases associated in Patients with Bernard-Soulier Syndrome, their ages ranged from 1 to 70 years. They had platelet counts from 22 to 178 × 10 9 /L. The mean value of MPV was 12.6 fL, with a range from 10.4 to 17.2 fL [92].
For response criteria in refractory ITP, see Table 9. Table 8:-Individual agents for treatment of ITP and the time to the first and peak responses if using the reported dose range [30] Agent/treatment Reported dose range Time to initial response* Time to peak response* Prednisone [46,47] 1-4 mg/kg PO daily x 1-4 wk 4-14 d 7-28 d Dexamethasone [48,49] 40 mg PO or IV daily x 4 d for 4-6 courses every 14-28 d

2-14 d 4-28 d
IVIg [50,51,52] 0.4-1 g/kg per dose IV (1-5 doses) Anti-D [53,54] 75 ug/kg per dose IV 1-3 d 3-7 d Rituximab [55,56,57] 375 mg/m2 per dose IV (4 weekly doses) 7-56 d 14-180 d Splenectomy [58] Laparoscopic 1-56 d 7-56 d Vincristine [46] up to 2 mg/dose IV (4-6 weekly doses)  [61,41,42] 3-10 ug/kg weekly SC 5-14 d 14-60 d Eltrombopag [43] 50-75 mg PO daily 7-28 d 14-90 d In the times to the initial and peak responses, the first number of days is the first time that a response could be reasonably expected and the second number of days is the time after which a response to this particular agent becomes less likely when administered at the dose and schedule listed in the table. Dosages, where not given on kilogram/body weight basis, are intended for adults. PO indicates per oral administration; IV, intravenous infusion; and SC, subcutaneous infusion. Table 9:-Refractory ITP [30] Definition (all should be met) Failure to achieve at least R or loss of R aftersplenectomy* Need of treatment(s) (including, but not limited to, low dose of corticosteroids) to minimize the risk of clinically significant bleeding. † Need of on-demand or adjunctive therapy alone does not qualify the patient as refractory. Primary ITP confirmed by excluding other supervened causes of thrombocytopenia. Definition of on-demand therapy Any therapy used to temporarily increase the platelet count sufficiently to safely perform invasive procedures or in case of major bleeding or trauma ‡ Definition of adjunctive therapy Any non-ITP specific therapy that may decrease bleeding (e.g., antifibrinolytic agents, hormonal agents, DDAVP, recombinant factor VIIa, fibrin sealants). Platelet transfusion is also included. Definition of response to therapy in refractory ITP Ability to maintain a platelet count sufficient to prevent clinically significant bleeding † § Ability to decrease toxic therapy (e.g., corticosteroids) does not qualify for response but should be reported Definition of response to on-demand therapy Control of bleeding in the specific situation Achievement of a platelet count sufficient to perform procedure or minimize bleeding from trauma DDAVP indicates deamino arginine vasopressin. *May not be applicable in children or in patients with accessory spleen. †Bleeding symptoms measured by a validated scale whenever possible (requires further studies). ‡Specific platelet thresholds cannot be provided, but in most instances, a platelet count of 50-70 x 10 9 /L would fulfill this criterion. §A strict definition of response in terms of predefined platelet count cannot be given and may not be appropriate when considering the risk/benefit ratio in refractory ITP, because the trade off between efficacy of a specific treatment and its short-and long-term toxicity varies among patients.