Clinical Profiles of BSS Patients
| Case No. . | Year-150 . | Platelet Count-151 . | Clinical Description . | Genetic Defect . | Ref. . |
|---|---|---|---|---|---|
| 1 | 1948 | 15-45 | French male. BSS index case. Presented at age 15 days with epistaxis and anal hemorrhage, then frequent bruising, GI bleeding. Later bleeding from trauma, including bilateral scrotal hematoma and severe epistaxis. BT >20 min. Died of cerebral hemorrhage at 28. Sister died at 31 mo of prolonged bleeding. Parents, other siblings unaffected. | Unknown | 1, 160 |
| 2 | 1974 | 75-280 | African-American male. Recurrent mucosal bleeding, giant platelets, BT >20 min. Female first cousin also BSS, with excessive menstrual and postpartum hemorrhage. In both cases, bleeding responded to platelet transfusions. | GP Ibα, homo. CTC → CCC, Leu129 → Pro. | 5, 200 |
| 3 | 1976 | 110 | French female. Severe hemorrhage during pregnancy; 3 successive miscarriages. Giant platelets, BT >20 min, no RIPA. | Unknown | 160 |
| 4 | 1976 | 80 | Greek female. Epistaxis, menorrhagia, and severe hemorrhage after teeth extractions. Giant platelets, BT >20 min, no RIPA. | Unknown | 160 |
| 5 | 1979 | French male. Long BT, large platelets, lack of platelet aggregation to ristocetin or bovine vWf. | Unknown | 203 | |
| 6 | 1980 | Female. Giant platelets and absent RIPA. BT >12 min. | Unknown | 204 | |
| 7 | 1981 | 66 | Caucasian female. Considered normal until severe bleeding from minor scalp laceration at age 1. Severe GI hemorrhage at age 4. Easy bruising and frequent epistaxis. Required transfusion on menarche at age 11, menstrual bleeding controlled by OCP. Vaginal delivery supported by platelet transfusions. BT >20 min. Brother also BSS, required transfusion following circumcision. Easy bruising, gingival bleeding, and severe epistaxis requiring transfusions approximately every 3 mo as a child. BT >20 min. Iron deficient. Sister unaffected. Parents (third cousins) are of German ancestry with no or minor bleeding. | GP Ibα, homo. Dinucleotide deletion (TAT) at Tyr492; Silent A → G at Arg342; T → C at −5 of 5′ UTR. | 120, 205 |
| 8 | 1981 | 50 | Kuwaiti female. Bleeding from gums, palate at 2 mo, regular transfusions throughout childhood. Severe prolonged bleeding at age 6 (tooth extractions) and age 13 (menarche, controlled by OCP). Major problem was constant gingival oozing. BT >20 min. Sister had epistaxis at age 3 and transfusions at age 6 (tooth extractions) and age 14 (menarche). Symptoms milder than proband, despite platelet count of 20,000/μL and BT >20 min. Eight other siblings and parents (first cousins) are normal. | Unknown | 3, 205 |
| 9 | 1982 | 39-72 | Swiss female. Bleeding episodes and absent RIPA, normal response to other agonists. Giant platelets, BT = 8 min. | Unknown | 12 |
| 10 | 1982 | French female. Thrombocytopenia, giant platelets. BT >30 min, platelet count normal following splenectomy. Absent RIPA. | Unknown | 12 | |
| 11 | 1982 | French male. Thrombocytopenia, BT >30 min. Platelets slightly larger than normal. No RIPA at low ristocetin concentration, ∼20% normal response at 1.4-3 mg/mL. | Unknown | 12 | |
| 12 | 1983 | 70-90 | Caucasian female. Life-long history of bruising, epistaxis and profuse bleeding. Severe menorrhagia until started on OCP. Giant platelets, lack of ristocetin- and bovine vWF-dependent aggregation. Brother also BSS, parents (first cousins) are normal. | Unknown | 13 |
| 13 | 1983 | 70-90 | Caucasian female. Life-long history of bruising, epistaxis and profuse bleeding. Mentally retarded, thrombocytopenia, ∼7% of normal GP Ib level. | Unknown | 13 |
| 14 | 1984 | 30-60 | French-Canadian family. Severe epistaxis, hemorrhage after dental surgery. BSS in 4 brothers and 3 sisters, the latter also menorrhagic. One sister experienced prolonged hemorrhage after cone biopsy of cervix. Increased BT, giant platelets, no RIPA. | Unknown | 206, 207 |
| 15 | 1985 | 60-100 | Afrikaner female. Spontaneous tonsillar hemorrhage at age 5, frequent epistaxis, prolonged bleeding after tooth extractions. Excessive menstrual bleeding controlled by OCP. Gross morphological platelet abnormalities, many “bizarre and giant forms.” Sister and two brothers also with BSS, two other brothers normal. Mother's family “bleeders.” Sister had near-fatal bleeding during childbirth. Affected siblings required lifelong transfusions; in adulthood, only following surgical procedures or severe trauma. Splenectomy in proband and two siblings appeared to reduce the number of severe bleeding episodes. | Unknown | 158 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 16 | 1985 | 120 | Afrikaner female. History of excessive and prolonged bleeding from childhood following minor injury. Marked menorrhagia. Transfusions required for tooth extractions, surgical procedures, after dilation and curettage and a thyroidectomy at age 21. | Unknown | 158 |
| 17 | 1986 | 81 | Male. Bolzano variant. Life-long history of epistaxis and gingival bleeding. Bleeding episodes continued after splenectomy at age 9 for thrombocytopenia. BT = 9 min. Sister died at age 2 from intracranial bleeding. Patient also homozygous for Thr145 → Met Koa polymorphism. Parents normal. | GP Ibα, homo. GCT → GTT, Ala156 → Val. | 76, 208 |
| 18 | 1986 | 62 | Male. History of easy bruising, ecchymoses, and profuse bleeding from cuts. Mother bruises easily, father asymptomatic. | Unknown | 208 |
| 19 | 1987 | 38-67 | Male. History of subcutaneous hematomas following injury. Prolonged bleeding after appendectomy. BT >15 min. Large platelets, no RIPA. Brother also BSS. No family history of bleeding. | Unknown | 209 |
| 20 | 1987 | 100 | Swiss female. Suffered from epistaxis, gingival bleeding, ecchymoses, frequent menorrhagia. Splenectomy and steroid treatment for suspected ITP ineffective. Giant platelets and no RIPA. Six other family members heterozygous for BSS. | Unknown | 167 |
| 21 | 1988 | 10-30 | French-Canadian brother and sister with BSS, parents and other sister are normal. | Unknown | 206 |
| 22 | 1988 | 25-100 | Male. Life-long history of easy bruising, recurrent epistaxis and occasional petechiae. Giant platelets, no aggregation to ristocetin or bovine vWF. Presented at age 14 with thrombocytopenia and bleeding following tooth extraction; required blood and platelet transfusions. Initially diagnosed as ITP; ineffective prednisolone treatment. At age 18, elective splenectomy lessened severity of subsequent epistaxis. DDAVP apparently shortened bleeding time. | Unknown | 168 |
| 23 | 1988 | 25-30 | Caucasian female. Life-long history of easy bruising, frequent epistaxis, occasional gum bleeding, and menorrhagia. Prolonged bleeding after dental extractions. Large platelets, BT >20 min. Refractory to platelets from random donors. Developed three red cell alloantibodies secondary to transfusions. OCP controlled menorrhagia and resulted in “less bruising and less frequent epistaxes.” DDAVP treatment was apparently ineffective. Sister also with BSS. | Unknown | 159 |
| 24 | 1989 | 28 | Caucasian female. Multiple blood or platelet transfusions after trauma or surgery. Abnormal RIPA, giant platelets. Hospitalized at 32 wk gestation, pelvic ultrasound showed fetal ascites and pericardial effusion. Isoimmunity suppressed by steroids and i.v. gamma globulin. Plasmapheresis allowed additional platelet transfusion. Gingival bleeding and ecchymotic suprapubic amniocentesis site. Amniocentesis led to premature membrane rupture. Chorioamnionitis 3 days later resulted in spontaneous labor (platelet count 8,000/μL). Excessive vaginal bleeding 3 wk after caesarean delivery; hysterectomy. Brother also with BSS. Parents second cousins. | Unknown | 161 |
| 25 | 1989 | 7-138 | Male. Life-long abnormal bleeding, prolonged gingival bleeding. Uncomplicated cesarean birth and circumcision. Thrombocytopenia (45,000/μL) at age 14 mo, BT >21 min. Splenectomy at age 3. Recurrent childhood epistaxis and ecchymoses, excused from physical education. Bleeding symptoms decreased at puberty, bled from tooth extractions at age 23. Worked as meatcutter from age 20 without major bleeding episodes. At age 30, painless upper GI bleeding required transfusions, as did facial lacerations following car accident. Brother, sister, and two children normal; no family history of bleeding. | Unknown | 210 |
| 26 | 1990 | Female. Excessive bleeding after tonsillectomy, menorrhagia, epistaxis and profuse bleeding associated with ear piercing. Younger brother also BSS with frequent epistaxis, once requiring hospitalization. Parents, two other siblings and five children normal. | Unknown. Probably not GP Ibα defect based on RFLP. | 211 | |
| 27 | 1990 | 25 | Spanish male. Life-long mucocutaneous bleeding, BT >30 min. Thrombocytopenia progressively worse from 120,000/μL in 1976. Splenectomy at age 6. Other family members normal. | GP Ibα, homo. TGC → AGC, Cys209 → Ser. | 199, 212 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 28 | 1990 | 32 | Male. Life-long bleeding tendency, frequent spontaneous epistaxes and mucosal hemorrhages requiring transfusions. Giant platelets with prominent granulations. | GP Ibα, hetero. TGG → TGA, Trp343 → stop in one allele, other defect unknown. | 198 |
| 29 | 1990 | 48 | Danish female. Frequent epistaxes, ∼30% normal level of GP Ibα. BT = 11 min. No RIPA. Sisters aged 19 and 9 also BSS, BTs of 12 and 13 min, respectively. One sister bled profusely following dental extractions. | Unknown | 213 |
| 30 | 1990 | 32 | Danish female. Microscopic hematuria, ∼7% normal level of GP Ibα. BT = 20 min (7 min at original diagnosis). No RIPA. Sister aged 71 also BSS, BT = 7 min. Consanguineous parents. | Unknown | 213 |
| 31 | 1990 | 47 | Danish female. Severe bleeding at delivery, GP Ibα ∼22% normal level. BT = 11.5 min, no RIPA. | Unknown | 213 |
| 32 | 1990 | 64 | Danish male. Numerous episodes of GI bleeding, ∼16% normal level of GP Ibα. BT = 8.5 min, no RIPA. | Unknown | 213 |
| 33 | 1991 | 51 | Swedish female. Mild hypothyroidism and, since age 6, insulin-dependent diabetes mellitus. At 30 mo, subcutaneous hematoma on forehead, incision resulted in week-long bleeding. Frequent epistaxes and profuse menstrual bleeding. At age 20, repeated blood transfusions for bleeding associated with IUD use. At age 32, anemia. Giant platelets, absent RIPA. BT >20 min, some response to DDAVP. Father and three brothers normal, mother with menorrhagia. | Unknown | 171 |
| 34 | 1991 | 10-65 | Swedish male, Karlstad variant. Thrombocytopenia from early childhood, life-long bleeding symptoms, severe gastric hemorrhage, subcutaneous hematomas, epistaxes and easy bruising. Bilateral subdural hematomas following violent sneeze. Giant platelets, no RIPA, low GP Ibα by flow cytometry. Corticosteroid treatment for ITP was ineffective and was discontinued. Splenectomy resulted in increased platelet count from 40,000 to 65,000/μL. BT >20 min, some beneficial effect of DDAVP. Normal number of megakaryocytes in bone marrow. Mother died of puerperal hemorrhage at childbirth. Parents with common ancestry from late seventeenth century. | GP Ibα, homo. TGG → TGA, Trp498 → stop. | 122, 171 |
| 35 | 1992 | 80 | Caucasian male. Frequent epistaxes, once resulting in hospitalization. Diagnosed prior to dental extraction because of thrombocytopenia. Mother had long history of bleeding, including bleeding associated with tonsillectomy, epistaxes, severe menorrhagia requiring hysterectomy, and GI bleeding. Autosomal dominant. | GP Ibα, hetero. CTC → TTC, Leu57 → Phe. | 75 |
| 36 | 1993 | Female. Life-long bleeding tendency, frequent episodes of mucosal bleeding, particularly melena. Two siblings affected, one sister unaffected. Giant platelets, no RIPA, membrane GP Ib deficient by immunostaining. | GP IX, compound hetero. GAC → GGC, Asp21 → Gly; AAC → AGC, Asn45 → Ser. | 114 | |
| 37 | 1993 | Japanese female. General anaesthesia induced by fentanyl and diazepam, and maintained with nitrous oxide, fentanyl and 0.5% enflurane without exacerbating the bleeding tendency. | Unknown | 173 | |
| 38 | 1994 | 24 | Japanese female. Diagnosed BSS by giant platelets, no RIPA, thrombocytopenia and GP Ib deficiency. BT = 15 min. Parents normal, elder sister also with BSS. Parents consanguineous. | GP Ibα, homo. TCA → TAA, Ser444 → stop. | 197 |
| 39 | 1994 | 30-60 | Caucasian male. Life-long bleeding tendency and epistaxes. Giant platelets, no RIPA and increased BT. Mother had mild bleeding, father and sister normal, brother with mild thrombocytopenia but no bleeding. | GP IX, homo. AAC → AGC, Asn45 → Ser. | 214 |
| 40 | 1994 | 35 | Caucasian male. Severe life-long bleeding, mainly epistaxes and hematomas requiring multiple blood transfusions. Giant platelets, BT >20 min. Splenectomy at age 4 decreased bleeding tendency and obviated transfusions, but severe epistaxis returned at age 37 associated with physical exertion. Controlled by intranasal tranexamic acid. | GP Ibα, homo. Deletion of T in codon 76, frame shift and truncation after 19 residues. | 172 |
| 41 | 1994 | 75 | Japanese female. Spontaneous epistaxes from early childhood, menorrhagia. ITP diagnosed at age 16, ineffective corticosteroid therapy and splenectomy. Giant platelets, no RIPA, GP Ib deficient by SDS-PAGE. Brother has mild thrombocytopenia, but no bleeding. Parents consanguineous. | GP IX, homo. TGG → TGA, Trp126 → stop. | 116, 215 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 42 | 1994 | 58 | Male. Thrombocytopenia and prolonged BT not corrected by DDAVP or tranexamic acid. History of mild purpura and an episode of prolonged gingival bleeding following a blow to the mouth at age 2. Steroid treatment ineffective. Brother diagnosed as ITP at age 4 after severe hematemesis, intermittent petechiae. Both brothers no RIPA, BT >15 min. Parents normal. | Unknown | 169 |
| 43 | 1994 | 65 | Female. Petechiae, giant platelets, no RIPA. BT >45 min, decreased to 6.5 min for 4-5 h after i.v. DDAVP. Sister also BSS, platelet count 45,000/μL, BT = 18 min (5 min after DDAVP). | Unknown | 174 |
| 44 | 1995 | 100-150 | Male. Nancy I variant. Life-long bleeding, bruising and epistaxes requiring platelet and erythrocyte transfusions, BT >10 min. Giant platelets and no RIPA. Brother and sister also affected. Parents and other brother normal. | GP Ibα, homo. CTC (Leu179) deleted. | 216 |
| 45 | 1995 | 42 | Japanese female. Severe menorrhagia and life-long bleeding. Initially diagnosed as ITP, ineffective corticosteroid therapy and splenectomy. Diagnosed as BSS at age 26 by low platelet count, giant platelets, no RIPA and GP Ib deficiency. At ages 27 and 29, vaginal childbirth accompanied by platelet transfusions. Parents consanguineous. | GP Ibα, homo. One base deletion in AAAAAAA sequence, 58-residue frame shift and premature stop. | 116 |
| 46 | 1995 | 83 | Male. Velo-cardio-facial syndrome with neonatal mild congestive heart failure due to conoventricular septal defect, thrombocytopenia. Abnormal bleeding from cardiac catheterization (18 mo) and circumcision (age 3), recurrent otitis media, delayed speech. Large platelets, diminished RIPA, epistaxis. Markedly low GP Ibα by flow cytometry. | GP Ibβ, compound hetero. C → G mutation at −133 (GATA site), other β allele deleted. | 182 |
| 47 | 1995 | Male. Diagnosed at age 7 with severe mucocutaneous hemorrhage. Low platelet count, giant platelets and reduced prothrombin consumption. History of repeated epistaxes and severe post-traumatic hemorrhage. Many platelet transfusions led to anti-HLA and anti-GP Ib alloimmunization and hepatitis B and C infection. Hospitalized due to severe anemia and intermittent melena. Upper endoscopy revealed esophagogastric ecchymoses, angiodysplasia of the duodenum, and vascular ectasias and purpuric ecchymoses of cecum and colon. | Unknown | 217 | |
| 48 | 1996 | Japanese female. Bleeding tendency since childhood, menorrhagia. Found to be thrombocytopenic at second pregnancy (age 27), no RIPA, giant platelets. Childbirth accompanied by platelet transfusion. Sister also BSS. Parents first cousins. | GP IX, homo. TGT → TAT, Cys73 → Tyr. | 121 | |
| 49 | 1996 | Japanese male. Life-long bleeding, episodes of severe spontaneous epistaxes. Diagnosed as ITP (aged 9), prednisolone without effect. At age 23, bled in lungs and diagnosed BSS. Giant platelets, no RIPA, low GP Ib levels. Father also BSS, paternal aunt died of blood loss, aged 7. Parents and paternal grandparents consanguineous. | GP IX, homo. TGT → TAT, Cys73 → Tyr. | 121 | |
| 50 | 1996 | 30-50 | Caucasian male. Bleeding disorder from early childhood, bled from tonsillectomy. Near-fatal bleeding as adult from splenectomy for suspected ITP. Recurrent bruising and severe GI bleeding often requiring hospitalization and blood or platelet transfusion. Treated with ε-aminocaproic acid. BT >20 min. Mother, sister, daughter normal. Parents consanguineous. | GP Ibα, homo. AAG → AGA, Lys19 → Arg due to A deletion, frame shift, stop at codon 21. | 170 |
| 51 | 1997 | 183-246 | Japanese female. Variant form of BSS. Frequent spontaneous epistaxes during childhood. Later, bleeding tendency diminished and no epistaxes or menorrhagia. Giant platelets, BT = 9.5 min, no RIPA or botocetin-induced aggregation in PRP. Both near normal with washed platelets. Diagnosed with type 2A vWD. GP Ibβ not disulfide linked to GP Ibα. Younger sister clinically similar. Parents with no bleeding history. Mother's platelets moderately enlarged, father's normal. | GP Ibβ, compound hetero. TAC → TGC, Tyr88 → Cys; GCC → CCC, Ala108 → Pro. | 183 |
| 52 | 1997 | 60 | Japanese female. History of bleeding, recurrent epistaxes, and melena from early childhood. Giant platelets, no RIPA, BT >15 min. Parents consanguineous. No family history of bleeding. | GP Ibα, homo. TG deletion at 972-975 of gene, frame shift after Thr294, premature stop. | 218 |
| 53 | 1997 | 25 | Japanese male. History of recurrent epistaxes and melena from early childhood. Giant platelets, BT >15 min. Parents consanguineous. No family history of bleeding, but father had low platelet count. | GP Ibα. compound hetero. T insertion at 1418; A deletion in AAAAAAA (1438-44), truncation. Both lead to premature termination. | 218 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 54 | 1997 | 50-75 | Male. Life-long bleeding tendency, spontaneous epistaxes up to age 20, then decreased. Splenectomy at age 24. After age 35, gingival bleeding with variable frequency and severity. Melena over 6 wk period at age 43 required hospitalization, but not transfusions. Giant platelets, no RIPA, BT = 4.5-6 min. Parents (first cousins) with no bleeding history. | GP IX, homo. TTT → TCT Phe55 → Ser in leucine-rich repeat. | 219 |
| 55 | 1997 | 20-30 | Caucasian male. Mother and paternal grandfather of German descent. Large platelets and profuse bleeding tendency requiring frequent transfusions. No RIPA. BT >15 min. Large amounts of glycocalicin in plasma. Brother and sister were normal. | Same as case 7. | 176 |
| Case No. . | Year-150 . | Platelet Count-151 . | Clinical Description . | Genetic Defect . | Ref. . |
|---|---|---|---|---|---|
| 1 | 1948 | 15-45 | French male. BSS index case. Presented at age 15 days with epistaxis and anal hemorrhage, then frequent bruising, GI bleeding. Later bleeding from trauma, including bilateral scrotal hematoma and severe epistaxis. BT >20 min. Died of cerebral hemorrhage at 28. Sister died at 31 mo of prolonged bleeding. Parents, other siblings unaffected. | Unknown | 1, 160 |
| 2 | 1974 | 75-280 | African-American male. Recurrent mucosal bleeding, giant platelets, BT >20 min. Female first cousin also BSS, with excessive menstrual and postpartum hemorrhage. In both cases, bleeding responded to platelet transfusions. | GP Ibα, homo. CTC → CCC, Leu129 → Pro. | 5, 200 |
| 3 | 1976 | 110 | French female. Severe hemorrhage during pregnancy; 3 successive miscarriages. Giant platelets, BT >20 min, no RIPA. | Unknown | 160 |
| 4 | 1976 | 80 | Greek female. Epistaxis, menorrhagia, and severe hemorrhage after teeth extractions. Giant platelets, BT >20 min, no RIPA. | Unknown | 160 |
| 5 | 1979 | French male. Long BT, large platelets, lack of platelet aggregation to ristocetin or bovine vWf. | Unknown | 203 | |
| 6 | 1980 | Female. Giant platelets and absent RIPA. BT >12 min. | Unknown | 204 | |
| 7 | 1981 | 66 | Caucasian female. Considered normal until severe bleeding from minor scalp laceration at age 1. Severe GI hemorrhage at age 4. Easy bruising and frequent epistaxis. Required transfusion on menarche at age 11, menstrual bleeding controlled by OCP. Vaginal delivery supported by platelet transfusions. BT >20 min. Brother also BSS, required transfusion following circumcision. Easy bruising, gingival bleeding, and severe epistaxis requiring transfusions approximately every 3 mo as a child. BT >20 min. Iron deficient. Sister unaffected. Parents (third cousins) are of German ancestry with no or minor bleeding. | GP Ibα, homo. Dinucleotide deletion (TAT) at Tyr492; Silent A → G at Arg342; T → C at −5 of 5′ UTR. | 120, 205 |
| 8 | 1981 | 50 | Kuwaiti female. Bleeding from gums, palate at 2 mo, regular transfusions throughout childhood. Severe prolonged bleeding at age 6 (tooth extractions) and age 13 (menarche, controlled by OCP). Major problem was constant gingival oozing. BT >20 min. Sister had epistaxis at age 3 and transfusions at age 6 (tooth extractions) and age 14 (menarche). Symptoms milder than proband, despite platelet count of 20,000/μL and BT >20 min. Eight other siblings and parents (first cousins) are normal. | Unknown | 3, 205 |
| 9 | 1982 | 39-72 | Swiss female. Bleeding episodes and absent RIPA, normal response to other agonists. Giant platelets, BT = 8 min. | Unknown | 12 |
| 10 | 1982 | French female. Thrombocytopenia, giant platelets. BT >30 min, platelet count normal following splenectomy. Absent RIPA. | Unknown | 12 | |
| 11 | 1982 | French male. Thrombocytopenia, BT >30 min. Platelets slightly larger than normal. No RIPA at low ristocetin concentration, ∼20% normal response at 1.4-3 mg/mL. | Unknown | 12 | |
| 12 | 1983 | 70-90 | Caucasian female. Life-long history of bruising, epistaxis and profuse bleeding. Severe menorrhagia until started on OCP. Giant platelets, lack of ristocetin- and bovine vWF-dependent aggregation. Brother also BSS, parents (first cousins) are normal. | Unknown | 13 |
| 13 | 1983 | 70-90 | Caucasian female. Life-long history of bruising, epistaxis and profuse bleeding. Mentally retarded, thrombocytopenia, ∼7% of normal GP Ib level. | Unknown | 13 |
| 14 | 1984 | 30-60 | French-Canadian family. Severe epistaxis, hemorrhage after dental surgery. BSS in 4 brothers and 3 sisters, the latter also menorrhagic. One sister experienced prolonged hemorrhage after cone biopsy of cervix. Increased BT, giant platelets, no RIPA. | Unknown | 206, 207 |
| 15 | 1985 | 60-100 | Afrikaner female. Spontaneous tonsillar hemorrhage at age 5, frequent epistaxis, prolonged bleeding after tooth extractions. Excessive menstrual bleeding controlled by OCP. Gross morphological platelet abnormalities, many “bizarre and giant forms.” Sister and two brothers also with BSS, two other brothers normal. Mother's family “bleeders.” Sister had near-fatal bleeding during childbirth. Affected siblings required lifelong transfusions; in adulthood, only following surgical procedures or severe trauma. Splenectomy in proband and two siblings appeared to reduce the number of severe bleeding episodes. | Unknown | 158 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 16 | 1985 | 120 | Afrikaner female. History of excessive and prolonged bleeding from childhood following minor injury. Marked menorrhagia. Transfusions required for tooth extractions, surgical procedures, after dilation and curettage and a thyroidectomy at age 21. | Unknown | 158 |
| 17 | 1986 | 81 | Male. Bolzano variant. Life-long history of epistaxis and gingival bleeding. Bleeding episodes continued after splenectomy at age 9 for thrombocytopenia. BT = 9 min. Sister died at age 2 from intracranial bleeding. Patient also homozygous for Thr145 → Met Koa polymorphism. Parents normal. | GP Ibα, homo. GCT → GTT, Ala156 → Val. | 76, 208 |
| 18 | 1986 | 62 | Male. History of easy bruising, ecchymoses, and profuse bleeding from cuts. Mother bruises easily, father asymptomatic. | Unknown | 208 |
| 19 | 1987 | 38-67 | Male. History of subcutaneous hematomas following injury. Prolonged bleeding after appendectomy. BT >15 min. Large platelets, no RIPA. Brother also BSS. No family history of bleeding. | Unknown | 209 |
| 20 | 1987 | 100 | Swiss female. Suffered from epistaxis, gingival bleeding, ecchymoses, frequent menorrhagia. Splenectomy and steroid treatment for suspected ITP ineffective. Giant platelets and no RIPA. Six other family members heterozygous for BSS. | Unknown | 167 |
| 21 | 1988 | 10-30 | French-Canadian brother and sister with BSS, parents and other sister are normal. | Unknown | 206 |
| 22 | 1988 | 25-100 | Male. Life-long history of easy bruising, recurrent epistaxis and occasional petechiae. Giant platelets, no aggregation to ristocetin or bovine vWF. Presented at age 14 with thrombocytopenia and bleeding following tooth extraction; required blood and platelet transfusions. Initially diagnosed as ITP; ineffective prednisolone treatment. At age 18, elective splenectomy lessened severity of subsequent epistaxis. DDAVP apparently shortened bleeding time. | Unknown | 168 |
| 23 | 1988 | 25-30 | Caucasian female. Life-long history of easy bruising, frequent epistaxis, occasional gum bleeding, and menorrhagia. Prolonged bleeding after dental extractions. Large platelets, BT >20 min. Refractory to platelets from random donors. Developed three red cell alloantibodies secondary to transfusions. OCP controlled menorrhagia and resulted in “less bruising and less frequent epistaxes.” DDAVP treatment was apparently ineffective. Sister also with BSS. | Unknown | 159 |
| 24 | 1989 | 28 | Caucasian female. Multiple blood or platelet transfusions after trauma or surgery. Abnormal RIPA, giant platelets. Hospitalized at 32 wk gestation, pelvic ultrasound showed fetal ascites and pericardial effusion. Isoimmunity suppressed by steroids and i.v. gamma globulin. Plasmapheresis allowed additional platelet transfusion. Gingival bleeding and ecchymotic suprapubic amniocentesis site. Amniocentesis led to premature membrane rupture. Chorioamnionitis 3 days later resulted in spontaneous labor (platelet count 8,000/μL). Excessive vaginal bleeding 3 wk after caesarean delivery; hysterectomy. Brother also with BSS. Parents second cousins. | Unknown | 161 |
| 25 | 1989 | 7-138 | Male. Life-long abnormal bleeding, prolonged gingival bleeding. Uncomplicated cesarean birth and circumcision. Thrombocytopenia (45,000/μL) at age 14 mo, BT >21 min. Splenectomy at age 3. Recurrent childhood epistaxis and ecchymoses, excused from physical education. Bleeding symptoms decreased at puberty, bled from tooth extractions at age 23. Worked as meatcutter from age 20 without major bleeding episodes. At age 30, painless upper GI bleeding required transfusions, as did facial lacerations following car accident. Brother, sister, and two children normal; no family history of bleeding. | Unknown | 210 |
| 26 | 1990 | Female. Excessive bleeding after tonsillectomy, menorrhagia, epistaxis and profuse bleeding associated with ear piercing. Younger brother also BSS with frequent epistaxis, once requiring hospitalization. Parents, two other siblings and five children normal. | Unknown. Probably not GP Ibα defect based on RFLP. | 211 | |
| 27 | 1990 | 25 | Spanish male. Life-long mucocutaneous bleeding, BT >30 min. Thrombocytopenia progressively worse from 120,000/μL in 1976. Splenectomy at age 6. Other family members normal. | GP Ibα, homo. TGC → AGC, Cys209 → Ser. | 199, 212 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 28 | 1990 | 32 | Male. Life-long bleeding tendency, frequent spontaneous epistaxes and mucosal hemorrhages requiring transfusions. Giant platelets with prominent granulations. | GP Ibα, hetero. TGG → TGA, Trp343 → stop in one allele, other defect unknown. | 198 |
| 29 | 1990 | 48 | Danish female. Frequent epistaxes, ∼30% normal level of GP Ibα. BT = 11 min. No RIPA. Sisters aged 19 and 9 also BSS, BTs of 12 and 13 min, respectively. One sister bled profusely following dental extractions. | Unknown | 213 |
| 30 | 1990 | 32 | Danish female. Microscopic hematuria, ∼7% normal level of GP Ibα. BT = 20 min (7 min at original diagnosis). No RIPA. Sister aged 71 also BSS, BT = 7 min. Consanguineous parents. | Unknown | 213 |
| 31 | 1990 | 47 | Danish female. Severe bleeding at delivery, GP Ibα ∼22% normal level. BT = 11.5 min, no RIPA. | Unknown | 213 |
| 32 | 1990 | 64 | Danish male. Numerous episodes of GI bleeding, ∼16% normal level of GP Ibα. BT = 8.5 min, no RIPA. | Unknown | 213 |
| 33 | 1991 | 51 | Swedish female. Mild hypothyroidism and, since age 6, insulin-dependent diabetes mellitus. At 30 mo, subcutaneous hematoma on forehead, incision resulted in week-long bleeding. Frequent epistaxes and profuse menstrual bleeding. At age 20, repeated blood transfusions for bleeding associated with IUD use. At age 32, anemia. Giant platelets, absent RIPA. BT >20 min, some response to DDAVP. Father and three brothers normal, mother with menorrhagia. | Unknown | 171 |
| 34 | 1991 | 10-65 | Swedish male, Karlstad variant. Thrombocytopenia from early childhood, life-long bleeding symptoms, severe gastric hemorrhage, subcutaneous hematomas, epistaxes and easy bruising. Bilateral subdural hematomas following violent sneeze. Giant platelets, no RIPA, low GP Ibα by flow cytometry. Corticosteroid treatment for ITP was ineffective and was discontinued. Splenectomy resulted in increased platelet count from 40,000 to 65,000/μL. BT >20 min, some beneficial effect of DDAVP. Normal number of megakaryocytes in bone marrow. Mother died of puerperal hemorrhage at childbirth. Parents with common ancestry from late seventeenth century. | GP Ibα, homo. TGG → TGA, Trp498 → stop. | 122, 171 |
| 35 | 1992 | 80 | Caucasian male. Frequent epistaxes, once resulting in hospitalization. Diagnosed prior to dental extraction because of thrombocytopenia. Mother had long history of bleeding, including bleeding associated with tonsillectomy, epistaxes, severe menorrhagia requiring hysterectomy, and GI bleeding. Autosomal dominant. | GP Ibα, hetero. CTC → TTC, Leu57 → Phe. | 75 |
| 36 | 1993 | Female. Life-long bleeding tendency, frequent episodes of mucosal bleeding, particularly melena. Two siblings affected, one sister unaffected. Giant platelets, no RIPA, membrane GP Ib deficient by immunostaining. | GP IX, compound hetero. GAC → GGC, Asp21 → Gly; AAC → AGC, Asn45 → Ser. | 114 | |
| 37 | 1993 | Japanese female. General anaesthesia induced by fentanyl and diazepam, and maintained with nitrous oxide, fentanyl and 0.5% enflurane without exacerbating the bleeding tendency. | Unknown | 173 | |
| 38 | 1994 | 24 | Japanese female. Diagnosed BSS by giant platelets, no RIPA, thrombocytopenia and GP Ib deficiency. BT = 15 min. Parents normal, elder sister also with BSS. Parents consanguineous. | GP Ibα, homo. TCA → TAA, Ser444 → stop. | 197 |
| 39 | 1994 | 30-60 | Caucasian male. Life-long bleeding tendency and epistaxes. Giant platelets, no RIPA and increased BT. Mother had mild bleeding, father and sister normal, brother with mild thrombocytopenia but no bleeding. | GP IX, homo. AAC → AGC, Asn45 → Ser. | 214 |
| 40 | 1994 | 35 | Caucasian male. Severe life-long bleeding, mainly epistaxes and hematomas requiring multiple blood transfusions. Giant platelets, BT >20 min. Splenectomy at age 4 decreased bleeding tendency and obviated transfusions, but severe epistaxis returned at age 37 associated with physical exertion. Controlled by intranasal tranexamic acid. | GP Ibα, homo. Deletion of T in codon 76, frame shift and truncation after 19 residues. | 172 |
| 41 | 1994 | 75 | Japanese female. Spontaneous epistaxes from early childhood, menorrhagia. ITP diagnosed at age 16, ineffective corticosteroid therapy and splenectomy. Giant platelets, no RIPA, GP Ib deficient by SDS-PAGE. Brother has mild thrombocytopenia, but no bleeding. Parents consanguineous. | GP IX, homo. TGG → TGA, Trp126 → stop. | 116, 215 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 42 | 1994 | 58 | Male. Thrombocytopenia and prolonged BT not corrected by DDAVP or tranexamic acid. History of mild purpura and an episode of prolonged gingival bleeding following a blow to the mouth at age 2. Steroid treatment ineffective. Brother diagnosed as ITP at age 4 after severe hematemesis, intermittent petechiae. Both brothers no RIPA, BT >15 min. Parents normal. | Unknown | 169 |
| 43 | 1994 | 65 | Female. Petechiae, giant platelets, no RIPA. BT >45 min, decreased to 6.5 min for 4-5 h after i.v. DDAVP. Sister also BSS, platelet count 45,000/μL, BT = 18 min (5 min after DDAVP). | Unknown | 174 |
| 44 | 1995 | 100-150 | Male. Nancy I variant. Life-long bleeding, bruising and epistaxes requiring platelet and erythrocyte transfusions, BT >10 min. Giant platelets and no RIPA. Brother and sister also affected. Parents and other brother normal. | GP Ibα, homo. CTC (Leu179) deleted. | 216 |
| 45 | 1995 | 42 | Japanese female. Severe menorrhagia and life-long bleeding. Initially diagnosed as ITP, ineffective corticosteroid therapy and splenectomy. Diagnosed as BSS at age 26 by low platelet count, giant platelets, no RIPA and GP Ib deficiency. At ages 27 and 29, vaginal childbirth accompanied by platelet transfusions. Parents consanguineous. | GP Ibα, homo. One base deletion in AAAAAAA sequence, 58-residue frame shift and premature stop. | 116 |
| 46 | 1995 | 83 | Male. Velo-cardio-facial syndrome with neonatal mild congestive heart failure due to conoventricular septal defect, thrombocytopenia. Abnormal bleeding from cardiac catheterization (18 mo) and circumcision (age 3), recurrent otitis media, delayed speech. Large platelets, diminished RIPA, epistaxis. Markedly low GP Ibα by flow cytometry. | GP Ibβ, compound hetero. C → G mutation at −133 (GATA site), other β allele deleted. | 182 |
| 47 | 1995 | Male. Diagnosed at age 7 with severe mucocutaneous hemorrhage. Low platelet count, giant platelets and reduced prothrombin consumption. History of repeated epistaxes and severe post-traumatic hemorrhage. Many platelet transfusions led to anti-HLA and anti-GP Ib alloimmunization and hepatitis B and C infection. Hospitalized due to severe anemia and intermittent melena. Upper endoscopy revealed esophagogastric ecchymoses, angiodysplasia of the duodenum, and vascular ectasias and purpuric ecchymoses of cecum and colon. | Unknown | 217 | |
| 48 | 1996 | Japanese female. Bleeding tendency since childhood, menorrhagia. Found to be thrombocytopenic at second pregnancy (age 27), no RIPA, giant platelets. Childbirth accompanied by platelet transfusion. Sister also BSS. Parents first cousins. | GP IX, homo. TGT → TAT, Cys73 → Tyr. | 121 | |
| 49 | 1996 | Japanese male. Life-long bleeding, episodes of severe spontaneous epistaxes. Diagnosed as ITP (aged 9), prednisolone without effect. At age 23, bled in lungs and diagnosed BSS. Giant platelets, no RIPA, low GP Ib levels. Father also BSS, paternal aunt died of blood loss, aged 7. Parents and paternal grandparents consanguineous. | GP IX, homo. TGT → TAT, Cys73 → Tyr. | 121 | |
| 50 | 1996 | 30-50 | Caucasian male. Bleeding disorder from early childhood, bled from tonsillectomy. Near-fatal bleeding as adult from splenectomy for suspected ITP. Recurrent bruising and severe GI bleeding often requiring hospitalization and blood or platelet transfusion. Treated with ε-aminocaproic acid. BT >20 min. Mother, sister, daughter normal. Parents consanguineous. | GP Ibα, homo. AAG → AGA, Lys19 → Arg due to A deletion, frame shift, stop at codon 21. | 170 |
| 51 | 1997 | 183-246 | Japanese female. Variant form of BSS. Frequent spontaneous epistaxes during childhood. Later, bleeding tendency diminished and no epistaxes or menorrhagia. Giant platelets, BT = 9.5 min, no RIPA or botocetin-induced aggregation in PRP. Both near normal with washed platelets. Diagnosed with type 2A vWD. GP Ibβ not disulfide linked to GP Ibα. Younger sister clinically similar. Parents with no bleeding history. Mother's platelets moderately enlarged, father's normal. | GP Ibβ, compound hetero. TAC → TGC, Tyr88 → Cys; GCC → CCC, Ala108 → Pro. | 183 |
| 52 | 1997 | 60 | Japanese female. History of bleeding, recurrent epistaxes, and melena from early childhood. Giant platelets, no RIPA, BT >15 min. Parents consanguineous. No family history of bleeding. | GP Ibα, homo. TG deletion at 972-975 of gene, frame shift after Thr294, premature stop. | 218 |
| 53 | 1997 | 25 | Japanese male. History of recurrent epistaxes and melena from early childhood. Giant platelets, BT >15 min. Parents consanguineous. No family history of bleeding, but father had low platelet count. | GP Ibα. compound hetero. T insertion at 1418; A deletion in AAAAAAA (1438-44), truncation. Both lead to premature termination. | 218 |
| Case No. | Year-150 | Platelet Count-151 | Clinical Description | Genetic Defect | Ref. |
| 54 | 1997 | 50-75 | Male. Life-long bleeding tendency, spontaneous epistaxes up to age 20, then decreased. Splenectomy at age 24. After age 35, gingival bleeding with variable frequency and severity. Melena over 6 wk period at age 43 required hospitalization, but not transfusions. Giant platelets, no RIPA, BT = 4.5-6 min. Parents (first cousins) with no bleeding history. | GP IX, homo. TTT → TCT Phe55 → Ser in leucine-rich repeat. | 219 |
| 55 | 1997 | 20-30 | Caucasian male. Mother and paternal grandfather of German descent. Large platelets and profuse bleeding tendency requiring frequent transfusions. No RIPA. BT >15 min. Large amounts of glycocalicin in plasma. Brother and sister were normal. | Same as case 7. | 176 |
Abbreviations: BSS, Bernard-Soulier syndrome; ITP, idiopathic thrombocytopenic purpura; OCP, oral contraceptive; PRP, platelet-rich plasma; BT, bleeding time (normal, <5 minutes); RIPAS, ristocetin-induced platelet aggregation; vWF, von Willebrand factor; vWD, von Willebrand disease.
Consanguinity of parents, where known, is also indicated.
Year first reported.
Platelet count × 10−3/μL (normal range, 150 to 250).