Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran

Figures & data

Table 1. Routine and specific coagulation tests available in Iranian coagulation laboratories [2,4,5].

General coagulation tests	Specific coagulation assays
Prothrombin time (PT)	Clauss fibrinogen assay
Activated partial thromboplastin time (APT)	Factor II assay
Thrombin time (TT)	Factor V assay
Reptilase time (RT)	Factor VII assay
Kaolin clotting time (KCT)	Factor VIII assay
Mixed prothrombin time (Mixed PT)	Factor X assay
Mixed activated partial thromboplastin time (mixed APTT)	Factor XI assay
Clot solubility test	–

Table 2. Characteristics of Iranian patients with RBDs.

Disorder	Number of patients (WFH)	Number of patients (literature^a)	Clinical presentations	Gene defects	Type of replacement therapy^b	Dose of treatment^b
FI deficiency	107	25	Umbilical cord bleeding Epistaxis GI bleeding Hematuria Intracranial hemorrhage	3282C→T 4209delA 4220delT	Prophylaxis	100 mg kg^−1 per every 2 weeks with CP
FII deficiency	24	4			On-demand	15–20 mL kg^−1 FFP
FV deficiency	147	96	Epistaxis Hematoma GI bleeding Post-partum bleeding Menorrhagia CNS bleeding Umbilical cord bleeding Recurrent miscarriage Hematuria Hemarthrosis	IVS8 + 6T > C IVS21 + 1G > A IVS24 + 1_ + 4delGTAG IVS19 + 3A > T	On-demand	FFP (15–20 mL kg^−1)
FV–VIII deficiency	190	95	Epistaxis Hemarthrosis CNS bleeding GI bleeding	c.822G > A c.904A > T (p.Lys302X) c.1261_1262insTG c.89–90insG	On-demand	FFP (15–30 mL kg^−1)
FVII deficiency	470	93	Epistaxis Post-dental extraction bleeding Hemarthrosis CNS bleeding	–	–	NM
FX deficiency	153	90	Epistaxis CNS bleeding Hemarthrosis GI bleeding Hematoma	Cys81Tyr Gly94Arg Asp95Glu Gly222Asp Glu69Lys Asp103His	Prophylaxis (Severe deficiency)	FFP (15–20 mL kg^−1)
FXI deficiency	152	53	Hemarthrosis Hematoma Epistaxis	1169G > C (Gly372Ala) 1693G > A (Glu547Lys) 403G > T (Glu117Stop)	On-demand	FFP (10 mL kg^−1)
FXIII deficiency	205	483	Umbilical cord bleeding Intracranial hemorrhage Miscarriage Hemarthrosis Hematoma	c562T > C (Trp187Arg) c320G > A (Arg77His) c868C > T (Arg260Cys) c869G > A (Arg260His) c1236G > T (Arg382Ser)	Prophylaxis	FFP: 10 mL kg^−1 every 28–30 days CP: One bag per 10–20 kg Fibrogammin: 10–26 IU/kg
FVII–FX deficiency	0	3	Umbilical cord bleeding GI bleeding Hematoma	FX: Ser3Cys FVII: Cys310Phe	–
FVII–FXIII deficiency	0	1	Umbilical cord bleeding	FXIII: Trp187Arg FVII: Unknown	Prophylaxis

^aReported cases may have some overlap because all studies did not mention precise origin of patients.

^bThese data are based on reference number 16.

Table 3. The comparisons between incidence of RBDs in Europe, Worldwide, and Iran. (https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Other-Factor-Deficiencies).

Missing factor	Incidence in Iran	Incidence worldwide	Incidence in Europe
Factor I Afibrinogenemia Hypofibrinogenemia Dysfibrinogenemia	1.7 in 1 000 000	1 or 2 in 1 000 000	5 in 10 000 000 Not available 1 in 1 000 000
Factor II	0.3 in 1 000 000	1 in 2 000 000	1 in 2 000 000
Factor V	2.3 in 1 000 000	1 in 1 000 000	1 in 1 000 000
Combined factor V and factor VIII	2.8 in 1 000 000	1 in 1 000 000	1 in 1 000 000
Factor VII	7.4 in 1 000 000	1 in 500 000	1 in 500 000
Factor X	2.1 in 1 000 000	1 in 500 000 to 1 000 000	1 in 1 000 000
Factor XI	2.4 in 1 000 000	1 in 100 000	1 in 100 000
Factor XIII	2.9 (6.5^a) in 1 000 000	1 in 2 000 000	1 in 3 000 000

^aAccording to reported number in the literature.

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