Rescue therapies in congenital VWD and AVWS associated with monoclonal gammopathy or autoimmune diseases
| Therapy patient no. . | Dose . | Outcome and follow-up . | Previous unsuccessful therapies . | Possiblemechanism . | Reference . |
|---|---|---|---|---|---|
| Estrogen/ progesterone | |||||
| 1 (type 2B VWD) | Estradiol patch (50 µg twice/wk for 3 wk on and 1 wk off), medroxyprogesterone acetate 5 mg/d (days 16-21) | Control of GI bleeding; follow-up, 11 mo | Not reported | VWF and FVIII increase | 30 |
| Danazol | |||||
| 2 (type 2B VWD) | 500 mg/d | Pt 1: control of GI bleeding but discontinued after 2 y for severe liver toxicity; follow-up, 6 y | Pt 1: VWF/FVIII concentrate prophylaxis, ε-aminocaproic acid, octreotide | FVIII increase | 31 |
| Pt 2: control of GI bleeding; follow-up, 18 mo | Pt 2: VWF/FVIII concentrate prophylaxis | ||||
| Tamoxifen | |||||
| 2 (type 3 VWD) | Not reported (possibly 20 mg/d) | Pt 1: control of GI bleeding; follow-up, 14 mo | Pt 1: VWF/FVIII concentrate prophylaxis, thalidomide, propranolol and isosorbide mononitrate, atorvastatin | Antiangiogenic effect | 32 |
| Pt 2: control of GI bleeding; follow-up, 10 mo (therapy stopped after 4 mo) | Pt 2: VWF/FVIII concentrate prophylaxis, statins | ||||
| Recombinant activated FVII | |||||
| 1 (type 1) | 80 µg/kg once daily during acute bleeding, associated with VWF/FVIII concentrate prophylaxis | Control of GI bleeding; follow-up, 2 y | Estrogen, desmopressin, tranexamic acid, VWF/FVIII concentrate prophylaxis, surgery | Activation of alternative hemostatic pathway | 33 |
| High-dose atorvastatin | |||||
| 1 (severe type 1 VWF) | 40 mg/d | Control of GI bleeding; follow-up, 12 mo | VWF/FVIII concentrate prophylaxis, thalidomide 100 mg/d discontinued for side effects, octreotide 20 mg/mo discontinued for lack of efficacy | Antiangiogenic effect at high dose | 34 |
| 1 (type 2A VWD) | 80 mg/d | Control of GI bleeding; follow-up, 14 mo | Ethinylestradiol, thalidomide | Antiangiogenic effect at high dose | 35 |
| Octreotide | |||||
| 2 (type 1, type 2A) | IV 500 µg for 2 d, 250 µg/thrice daily (subcutaneous), then tapered to lower dose | Pt 1: control of GI bleeding; follow-up, 13 mo | Pt 1: VWF/FVIII concentrate prophylaxis, tranexamic acid, desmopressin, high-dose estrogens | Reduction of splanchnic and portal blood flow | 36 |
| Pt 2: control of GI bleeding; follow-up, 6 mo | Pt 2: VWF/FVIII concentrate | ||||
| 1 (type 1 VWD) | 20 mg intramuscular every month | Control of GI bleeding (in association with propranolol 20 mg/3 times per day); follow-up, 8 mo | Desmopressin prophylaxis | Reduction of splanchnic and portal blood flow | 37 |
| Thalidomide | |||||
| 1 (type 2B VWD) | 150 mg/d | Control of GI bleeding; follow-up, 5 mo | Octreotide, discontinued for diarrhea | Antiangiogenic effect | 38 |
| 1 (type 2A) | 100 mg/d, increased to 150 mg/d for bleeding | Initial control of GI bleeding for 1 y, subsequent recurrence; follow-up, 22 mo | Desmopressin, tranexamic acid, VWF/FVIII concentrate | Antiangiogenic effect | 39 |
| 1 (type 2B) | 100 mg/d, decreased to 50 mg/d for fatigue | Control of GI bleeding (in association with estradiol/norethisterone, tranexamic acid), follow-up | VWF concentrate prophylaxis, recombinant activated FVII | Antiangiogenic effect | 40 |
| 1 (AVWS associated to IgG monoclonal gammopathy) | 50 mg/d | Control of GI bleeding; follow-up, 3 y | Desmopressin, VWF/FVIII concentrate, IV immunoglobulins, tranexamic acid, propranolol | Antiangiogenic effect | 41 |
| Lenalidomide | |||||
| 5 (3 type 3 VWD, 1 type 1 VWD, 1 type 2A VWD) | 5 mg/d for 3 wk on and 1 wk off, uptitrated to 10 and 15 mg/d if necessary (tapering to 2 wk on and 2 off when GI bleeding was obtained) | Control of GI bleeding; follow-up, 4-24 mo | Not reported | Antiangiogenic effect | 42 |
| 1 (AVWS associated to IgM monoclonal gammopathy) | 25 mg/d for 3 wk on and 1 wk off (decreased to 20 mg/d for 3 wk on and 1 wk off) | Control of GI bleeding; follow-up, 11 mo | Tranexamic acid, VWF/FVIII concentrate prophylaxis, plasma exchange, IV immunoglobulins, atorvastatin, octreotide, rituximab, and bendamustine | Antiangiogenic effect | 43 |
| Rituximab | |||||
| 2 (AVWS associated to monoclonal gammopathy) | Pt 1: 350 mg/m2 for 2 administrations | Not efficacious | Successful treatment with IV immunoglobulins | Anti-CD20, immunosuppressive effect | 44 |
| Pt 2: 350 mg/m2 for 4 administrations | |||||
| 1 (AVWS associated to systemic lupus erythematosus) | 375 mg/m2 biweekly in 2 doses | Control of GI bleeding and normalization of VWF levels | Steroid and cyclophosphamide | Anti-CD20, immunosuppressive effect | 45 |
| 1 (AVWS, characteristics not specified) | 375 mg/m2 weekly for 4 wk | Control of GI bleeding; follow-up, 5 mo | VWF concentrate, thalidomide; successful treatment with IV immunoglobulins | Anti-CD20, immunosuppressive effect | 46 |
| Therapy patient no. . | Dose . | Outcome and follow-up . | Previous unsuccessful therapies . | Possiblemechanism . | Reference . |
|---|---|---|---|---|---|
| Estrogen/ progesterone | |||||
| 1 (type 2B VWD) | Estradiol patch (50 µg twice/wk for 3 wk on and 1 wk off), medroxyprogesterone acetate 5 mg/d (days 16-21) | Control of GI bleeding; follow-up, 11 mo | Not reported | VWF and FVIII increase | 30 |
| Danazol | |||||
| 2 (type 2B VWD) | 500 mg/d | Pt 1: control of GI bleeding but discontinued after 2 y for severe liver toxicity; follow-up, 6 y | Pt 1: VWF/FVIII concentrate prophylaxis, ε-aminocaproic acid, octreotide | FVIII increase | 31 |
| Pt 2: control of GI bleeding; follow-up, 18 mo | Pt 2: VWF/FVIII concentrate prophylaxis | ||||
| Tamoxifen | |||||
| 2 (type 3 VWD) | Not reported (possibly 20 mg/d) | Pt 1: control of GI bleeding; follow-up, 14 mo | Pt 1: VWF/FVIII concentrate prophylaxis, thalidomide, propranolol and isosorbide mononitrate, atorvastatin | Antiangiogenic effect | 32 |
| Pt 2: control of GI bleeding; follow-up, 10 mo (therapy stopped after 4 mo) | Pt 2: VWF/FVIII concentrate prophylaxis, statins | ||||
| Recombinant activated FVII | |||||
| 1 (type 1) | 80 µg/kg once daily during acute bleeding, associated with VWF/FVIII concentrate prophylaxis | Control of GI bleeding; follow-up, 2 y | Estrogen, desmopressin, tranexamic acid, VWF/FVIII concentrate prophylaxis, surgery | Activation of alternative hemostatic pathway | 33 |
| High-dose atorvastatin | |||||
| 1 (severe type 1 VWF) | 40 mg/d | Control of GI bleeding; follow-up, 12 mo | VWF/FVIII concentrate prophylaxis, thalidomide 100 mg/d discontinued for side effects, octreotide 20 mg/mo discontinued for lack of efficacy | Antiangiogenic effect at high dose | 34 |
| 1 (type 2A VWD) | 80 mg/d | Control of GI bleeding; follow-up, 14 mo | Ethinylestradiol, thalidomide | Antiangiogenic effect at high dose | 35 |
| Octreotide | |||||
| 2 (type 1, type 2A) | IV 500 µg for 2 d, 250 µg/thrice daily (subcutaneous), then tapered to lower dose | Pt 1: control of GI bleeding; follow-up, 13 mo | Pt 1: VWF/FVIII concentrate prophylaxis, tranexamic acid, desmopressin, high-dose estrogens | Reduction of splanchnic and portal blood flow | 36 |
| Pt 2: control of GI bleeding; follow-up, 6 mo | Pt 2: VWF/FVIII concentrate | ||||
| 1 (type 1 VWD) | 20 mg intramuscular every month | Control of GI bleeding (in association with propranolol 20 mg/3 times per day); follow-up, 8 mo | Desmopressin prophylaxis | Reduction of splanchnic and portal blood flow | 37 |
| Thalidomide | |||||
| 1 (type 2B VWD) | 150 mg/d | Control of GI bleeding; follow-up, 5 mo | Octreotide, discontinued for diarrhea | Antiangiogenic effect | 38 |
| 1 (type 2A) | 100 mg/d, increased to 150 mg/d for bleeding | Initial control of GI bleeding for 1 y, subsequent recurrence; follow-up, 22 mo | Desmopressin, tranexamic acid, VWF/FVIII concentrate | Antiangiogenic effect | 39 |
| 1 (type 2B) | 100 mg/d, decreased to 50 mg/d for fatigue | Control of GI bleeding (in association with estradiol/norethisterone, tranexamic acid), follow-up | VWF concentrate prophylaxis, recombinant activated FVII | Antiangiogenic effect | 40 |
| 1 (AVWS associated to IgG monoclonal gammopathy) | 50 mg/d | Control of GI bleeding; follow-up, 3 y | Desmopressin, VWF/FVIII concentrate, IV immunoglobulins, tranexamic acid, propranolol | Antiangiogenic effect | 41 |
| Lenalidomide | |||||
| 5 (3 type 3 VWD, 1 type 1 VWD, 1 type 2A VWD) | 5 mg/d for 3 wk on and 1 wk off, uptitrated to 10 and 15 mg/d if necessary (tapering to 2 wk on and 2 off when GI bleeding was obtained) | Control of GI bleeding; follow-up, 4-24 mo | Not reported | Antiangiogenic effect | 42 |
| 1 (AVWS associated to IgM monoclonal gammopathy) | 25 mg/d for 3 wk on and 1 wk off (decreased to 20 mg/d for 3 wk on and 1 wk off) | Control of GI bleeding; follow-up, 11 mo | Tranexamic acid, VWF/FVIII concentrate prophylaxis, plasma exchange, IV immunoglobulins, atorvastatin, octreotide, rituximab, and bendamustine | Antiangiogenic effect | 43 |
| Rituximab | |||||
| 2 (AVWS associated to monoclonal gammopathy) | Pt 1: 350 mg/m2 for 2 administrations | Not efficacious | Successful treatment with IV immunoglobulins | Anti-CD20, immunosuppressive effect | 44 |
| Pt 2: 350 mg/m2 for 4 administrations | |||||
| 1 (AVWS associated to systemic lupus erythematosus) | 375 mg/m2 biweekly in 2 doses | Control of GI bleeding and normalization of VWF levels | Steroid and cyclophosphamide | Anti-CD20, immunosuppressive effect | 45 |
| 1 (AVWS, characteristics not specified) | 375 mg/m2 weekly for 4 wk | Control of GI bleeding; follow-up, 5 mo | VWF concentrate, thalidomide; successful treatment with IV immunoglobulins | Anti-CD20, immunosuppressive effect | 46 |
Pt, patient.