e98
LETTERS TO THE EDITORS
5 Auerswald G, Bidlingmaier C, Kurnik K. Early prophylaxis/FVIII tolerization regimen that avoids immunological danger signals is still effective in minimizing FVIII inhibitor developments in previously untreated patients–long-term follow-up and continuing experience. Haemophilia 2012; 18: e18–20. 6 Valentino LA, Hakobyan N, Kazarian T, Jabbar KJ, Jabbar AA. Experimental haemophilic synovitis: rationale and development
of a murine model of human factor VIII deficiency. Haemophilia 2004; 10: 280–7. 7 Ovlisen K, Kristensen AT, Jensen AL, Tranholm M. IL-1 beta, IL-6, KC and MCP-1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis. Haemophilia 2009; 15: 802–10. 8 Arnold WD, Hilgartner MW. Hemophilic arthropathy. Current concepts of pathogenesis and management. J Bone Joint Surg Am 1977; 59: 287–305.
9 Pfistershammer K, Stockl J, Siekmann J, Turecek PL, Schwarz HP, Reipert BM. Recombinant factor VIII and factor VIIIvon Willebrand factor complex do not present danger signals for human dendritic cells. Thromb Haemost 2006; 96: 309–16. 10 Astermark J, Altisent C, Batorova A et al. Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report. Haemophilia 2010; 16: 747–66.
Management of pregnancy in type 2B von Willebrand disease: case report and literature review E . B I G U Z Z I , * S . M . S I B O N I , * M . W . O S S O L A , † B . Z A I N A , † A . C . M I G L I O R I N I ‡ and F. PEYVANDI* *Angelo Bianchi Bonomi Hemophilia and Thrombosis Center IRCCS Ca’ Granda Maggiore Policlinico Hospital Foundation and University of Milan; †Department of Obstetrics and Gynecology; and ‡Laboratory of Haematology, IRCCS Fondazione Ca Granda Policlinico, University of Milan, Milan, Italy
von Willebrand disease (VWD) is a bleeding disorder characterized by quantitative or qualitative defects of the platelet-adhesive protein von Willebrand factor (VWF). Type 2B VWD is very characteristic because it is characterized by a dysfunctional VWF with increased affinity for the platelet receptor GP Ib-alpha and it may be characterized by moderate or severe thrombocytopenia. Federici et al. [1], reported thrombocytopenia in 30% of patients at baseline (increased to 57% of patients after stress or in case of bleeding episodes) and was associated with a higher risk of bleeding. The pathophysiology of thrombocytopenia was recently investigated and accelerated uptake of VWF/platelet complexes by macrophages and reduced platelet lifespan was described [2]. Furthermore, a specific mutation (V1316M) associated with type 2B VWD, clinically characterized by severe bleeding and thrombocytopenia, was recently shown [3] to be associated with severe thrombocytopathy (impairment of platelet aggregation, secretion and spreading due to inhibition of integrin alphaIIb betaIII). We report a type 2B VWD patient, diagnosed at the age of 8 years following investigations for severe epiCorrespondence: Eugenia Biguzzi, MD, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca’ Granda Maggiore Policlinico Hospital Foundation, via Pace 9, 20122 Milano, Italy. Tel.: +39 02 5503 5308; fax: +39 02 5503 5347; e-mail: [email protected] Accepted after revision 12 October 2014 DOI: 10.1111/hae.12580 Haemophilia (2015), 21, e70--e121
staxis. Laboratory parameters at diagnosis were as follows: bleeding time 100 50″, coagulant factor VIII (FVIII:C) 79%, VWF antigen (VWF:Ag) 64%, VWF Ristocetin cofactor activity (VWF:RCo) 22%, increased VWF ristocetin-induced platelet aggregation (VWF:RIPA), lack of high molecular weight VWF multimers, platelet count 146 9 109 L1, mutation p.R1308C. At the age of 37 years, the patient had an early foetal loss (9th week) and underwent revision of the uterine cavity, without any prophylaxis and no bleeding complications. At the age of 38 years, during her second pregnancy the patient received purified VWF concentrate (Wilfactin 25 U kg1 twice per week, from week 35 to week 37), albeit the absence of bleeding symptoms, because of severe thrombocytopenia (platelets 44 9 109 L1), that did not show any significant change after treatment (platelets ranging from 9 9 109 to 34 9 109 L1). At delivery (caesarean section at 38 weeks due to ‘unripe cervix for induction of labour’), the patient received one platelet transfusion (from HLA-matched single donor) with a good recovery of platelet number (65 9 109 L1, 1 h after transfusion), and Wilfactin 25 U kg1. FVIII:C and VWF:RCo were maintained between 100–147% and 70–100% respectively in the following 6 days (Wilfactin 12.5 U kg1 on day +3 and +6). VWF:RCo levels before and after treatment are shown in Fig. 1a. Haemoglobin level (13.5 g dL1 before surgery) decreased to 8.9 g dL1 and platelets count increased to 49 9 109 L1 at discharge from the hospital. Total consumption of Wilfactin was © 2014 John Wiley & Sons Ltd
LETTERS TO THE EDITORS (a1)
(b1)
2nd pregnancy: VWF:RCo
120
e99
3rd pregnancy: VWF:RCo
180
48 hs
160
100
140 120
%
%
80 60
100 80
40
60 40
20
20 0
0 35 week
36 week
37 week
cesarean day +3 section
Platelets
(a2)
31 week
35 week
cesarean section
Platelets
(b2)
70
60
60
50
50
40
x109/L
x10e3/mmc
33 week
40 30
30 20
20 10
10
0
0 35 week
36 week
37 week
cesarean day +3 section
31 week
33 week
35 week
cesarean section
Fig. 1. a1 and b1: VWF:RCo levels during 2nd and 3rd pregnancy. Vertical arrows indicate infusions of von Willebrand factor (VWF) concentrate (bolus), horizontal arrow indicates continuous infusion of VWF concentrate. a1 and b2: platelets values during 2nd and 3rd pregnancy. Arrows indicate platelet transfusions.
16 000 U (12 000 U before delivery, 2000 U before caesarean section and 2000 U in the postpartum period). A bleeding complication (subfascial haematoma) was ascertained 3 weeks after delivery, when the patient was evaluated by the obstetrician for pelvic pain; no surgical wound revision or substitutive therapy with VWF concentrate was necessary. A third pregnancy in 2013 (age 40 years), was characterized by thrombocytopenia: platelets 100 9 109 L1 at week 10, 46 9 109 L1 at week 19, 44 9 109 L1 at week 27. Because of low ferritin levels, albeit normal haemoglobin levels (Hb 12 g dL1), iron supplementation was started at 27 weeks. At 33 weeks, a mild increase in FVIII:C 91% and VWF:RCo 28% was associated with platelet count decrease (11 9 109 L1), associated with moderate gum bleeding that was treated with plasma-derived FVIII/VWF concentrate (Humate-P 25 FVIII U kg1). A blood film was performed showing platelet clumps and presence of giant platelets. For this reason, the platelet count was automatically repeated using the optical channel (49 9 109 L1). A second infusion of Humate-P (25 FVIII U kg1) was given at 35 weeks of gestation for gum bleeding again. In 36 + 4 week, haemoglobin was 13.6 g dL1, while © 2014 John Wiley & Sons Ltd
platelet count (automated optical method) dropped to 24 9 109 L1. A caesarean section was performed under general anaesthesia the following day. The patient was treated preoperatively with one platelet pool, intravenous tranexamic acid (1 g) and Humate-P (25 U FVIIII kg1). During surgery, continuous infusion of Humate-P was administrated (2 FVIII U kg1 h1). Good haemostatic control was observed during surgery, but subcutaneous oozing was noted at the end of surgery, with an estimated blood loss of 500 mL. Platelet count was evaluated 1 h after platelet pool administration, before the beginning of surgery, and showed no response to the transfusion (platelets before 32 9 109 L1, after 38 9 109 L1). FVIII:C and VWF:RCo were maintained above 100% for 48 h (progressive decrease and final stop of the continuous intravenous infusion). The patient received further treatments (Humate-P 25 FVIII U kg1) on days +4, +5, +7, +10. Total consumption of HumateP was 4000 U before delivery, 2000 U at caesarean section and 13 620 U after delivery. VWF:RCo levels before and after treatment are shown in Fig. 1b. Tranexamic acid was associated until day +7. Haemoglobin levels decreased for 13.6 g dL1 (prepartum) Haemophilia (2015), 21, e70--e121
e100
LETTERS TO THE EDITORS
Table 1. Data from the literature regarding pregnancy follow-up in patients affected by type 2B VWD. Patient – pregnancy
Author Rick et al. [4]
Casonato et al. [5]
1–2
2–2
Mutation
Age at delivery
Previous pregnancy with late foetal loss associated
Not reported
36
Planned caesarean section
Not reported
40 000
Not reported
Yes – number not reported
with hypertension Previous normal delivery
Not
33
Vaginal
Not reported
20 000 at delivery
Not reported
No
with mild bleeding 13 years ago Takafuta et al. [6]
Delivery
Delivery week
reported
Plt count/mmc
Anaesthesia
Prophylactic plt transfusion
Previous obstetrical history
(48 000 in day +2, 77 000 in day
3–1
p.R1308C
28
Caesarean section
42
+4) 130 000
Not reported
No
4–1
p.R1306W
26
Spontaneous vaginal
Not reported
72 000
Not reported
No
p.R1308C
34
Caesarean section
38
12 000
Not reported
No
26
Inducted vaginal delivery
36.5
17 000
Not reported
Yes – number not
(twin pregnancy) Vaginal
Not reported
Not reported
Not reported
reported No
Vaginal
39
25 000 (142 000 at
Notreported
Yes – 1 pool
5–2
Previous spontaneous delivery with important blood loss (1100 g) treated with transfusion (20 pool plt, 5 units
Foster [7]
6–1
fresh whole blood) Not reported
7–1
Not reported
7–2
Not reported
Burlingame et al.
8–1
[8] G€ uth et al., [9]
9–6
Not 5 vaginal delivery without bleeding complications, without prophylactic
reported Not
Not reported
reported
treatment 10 – 1
Not
30
reported
discharge)
Not reported Mathew et al. [10]
11 – 1
Not reported
Not reported
Not reported
Not eported
20 000
Not reported
No
Hepner et al. [11]
12 – 1
Not reported
33
Vaginal
39
20 000
None
No
35
Caesarean section
38
36 000
General
Yes – 1 pool without response +1 pool more
39
Labour induction, vaginal
39
31 000
Not reported
Yes – 1 pool with
12 – 2 pregnancy
De Wee et al., [12]
No data regarding
Ranger et al. [13]
deliveries in 15 patients 13 – 3 pregnancy
2 previous pregnancy
p.R1306W
losses at 7 weeks
14 – 1 pregnancy
delivery
p.R1306W
34
Urgent caesarean section
response (31 000 to >51 000) +6 more pools to maintain 38–39
126 000 (74 000 in
Spinal
plt counts >50 000 No
day +3)
14 – 2 pregnancy
15 – 3 pregnancy
2 previous deliveries with
p.R1306W
37
Elective caesarean section
39
48 000 (23 000 in day +1)
Not reported
Yes – 1 pool
p.R1308C
35
Caesarean section
38
278 000
General
No
p.P1337L
23
Vaginal
39
125 000
Epidural
No
p.R1308C
38
Caesarean section
38
27 000
General
Yes – 1 pool
p.R1308C
36 + 5
Caesarean section
38
32 000 (optical count)
General
Yes – 1 pool without response
important blood loss treated with transfusion and surgical intervention Lagarrigue et al.
16 – 1 pregnancy
[14]
Biguzzi et al., 2014
Not reported 17 – 2 pregnancy
Previous early foetal loss (9th week)
17 – 3 pregnancy
to 12.1 g dL1 (day +4 postpartum) and subsequently increased to 14.5 g dL1 (day +10 post partum). A progressive rise of platelet number was observed at day +4 (optical count 42 9 109 L1) and platelet count was 112 9 109 L1 at hospital discharge (day +10). No bleeding complications developed in the postpartum period. Antiembolism compression stockHaemophilia (2015), 21, e70--e121
ings were used during the first 5 days of the postpartum period. Ten case stories/series specifically reporting the management of type 2B VWD patients (n = 16) during pregnancy were published between 1987 and 2012 [4–13]. Table 1 summarizes patients’ characteristics and specific treatments. © 2014 John Wiley & Sons Ltd
LETTERS TO THE EDITORS
Prophylactic replacement therapy
Blood loss (mL)
Cryoprecipitate
1800
Fresh plasma before and
Not reported
Treatment: concentrate after delivery No
Transfusion/Other Not reported
Days of hospitalization
Total concentrate consumption for delivery
Readmission
Treatment during readmission
e101
DVT prophylaxis
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
after delivery
Humate-P 3000 U RCo
800
Haemate-P for 4
10 pool PLT
Not reported
Not reported
Not reported
Not reported
(42 U RCo kg1) No
1800
more days Haemate-P 4000 U RCo
Prostaglandin F2
Not reported
Haemate-P 4000 U
Not reported
Not reported
No
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Humate-P 2000 U RCo
700
(40 U Rco kg1) + 1000 U (20 U kg1)
Not specified FVIII concentrate 40–
(75 U RCo kg1) Haemate-P for 2 more days
No bleeding complications
60 U kg1
Not specified FVIII concentrate 40– 60 U kg1 for 7 days
No treatment
Bleeding complications
Multiple transfusions
Not reported
Not reported
Not reported
Not reported
No treatment
Bleeding complications
Multiple transfusions
Not reported
Not reported
Not reported
Not reported
Alphanate
Not reported
Not reported
Not reported
Not reported
No
No bleeding complications
Not reported
Not reported
Not reported
Humate-P
800 + 2000 (day +3)
3000 U + antifibrinolytic
Haemate-P
4 U RBC
Not reported
Haemate-P 5500 U
Not reported
1500 U + 1000 U dopo 6 ore Humate-P
No bleeding complications
Not reported
Humate-P 3000 U RCo (42 U kg1) – 1250 U
Not reported
Not reported
Not reported Humate-P 3000 U RCo (42 U kg1) – 1250 U
FVIII (18 U kg1) Humate-P 4200 U RCo – 1750 U FVIII
FVIII (18 U kg1) 1000
Humate-P 5000 U RCo every 12 h for
1 PLT pool
Yes – vaginal lacerations in day +5
Not reported Vaginal packing + RBC 4 units + Humate-P
Not reported
3000 U Rco + antifibrinolytic
Not reported
Humate-P 34 200 U Rco, 14 250 U FVIII
Not reported
Not reported
3 (80 000 plt at discarge)
Not reported
Not reported
Antiembolism
3 days
Regular infusion of
Not clinically significant
Humate-P
Desmopressin
compression stocking
500
Yes – pelvic pain
Not reported
Antibiotics only
Not reported
Surgical revision and haemostatic treatment
Antiembolism compression stocking
(presumed infected muscular haematoma) in day +10 Humate-P 25 U FVIII kg1
1000
Humate-P 30 U kg1 FVIII
900 (significant generalizedoozing at surgery)
Wilfactin 4000 U
LETTERS TO THE EDITORS
5 Auerswald G, Bidlingmaier C, Kurnik K. Early prophylaxis/FVIII tolerization regimen that avoids immunological danger signals is still effective in minimizing FVIII inhibitor developments in previously untreated patients–long-term follow-up and continuing experience. Haemophilia 2012; 18: e18–20. 6 Valentino LA, Hakobyan N, Kazarian T, Jabbar KJ, Jabbar AA. Experimental haemophilic synovitis: rationale and development
of a murine model of human factor VIII deficiency. Haemophilia 2004; 10: 280–7. 7 Ovlisen K, Kristensen AT, Jensen AL, Tranholm M. IL-1 beta, IL-6, KC and MCP-1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis. Haemophilia 2009; 15: 802–10. 8 Arnold WD, Hilgartner MW. Hemophilic arthropathy. Current concepts of pathogenesis and management. J Bone Joint Surg Am 1977; 59: 287–305.
9 Pfistershammer K, Stockl J, Siekmann J, Turecek PL, Schwarz HP, Reipert BM. Recombinant factor VIII and factor VIIIvon Willebrand factor complex do not present danger signals for human dendritic cells. Thromb Haemost 2006; 96: 309–16. 10 Astermark J, Altisent C, Batorova A et al. Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report. Haemophilia 2010; 16: 747–66.
Management of pregnancy in type 2B von Willebrand disease: case report and literature review E . B I G U Z Z I , * S . M . S I B O N I , * M . W . O S S O L A , † B . Z A I N A , † A . C . M I G L I O R I N I ‡ and F. PEYVANDI* *Angelo Bianchi Bonomi Hemophilia and Thrombosis Center IRCCS Ca’ Granda Maggiore Policlinico Hospital Foundation and University of Milan; †Department of Obstetrics and Gynecology; and ‡Laboratory of Haematology, IRCCS Fondazione Ca Granda Policlinico, University of Milan, Milan, Italy
von Willebrand disease (VWD) is a bleeding disorder characterized by quantitative or qualitative defects of the platelet-adhesive protein von Willebrand factor (VWF). Type 2B VWD is very characteristic because it is characterized by a dysfunctional VWF with increased affinity for the platelet receptor GP Ib-alpha and it may be characterized by moderate or severe thrombocytopenia. Federici et al. [1], reported thrombocytopenia in 30% of patients at baseline (increased to 57% of patients after stress or in case of bleeding episodes) and was associated with a higher risk of bleeding. The pathophysiology of thrombocytopenia was recently investigated and accelerated uptake of VWF/platelet complexes by macrophages and reduced platelet lifespan was described [2]. Furthermore, a specific mutation (V1316M) associated with type 2B VWD, clinically characterized by severe bleeding and thrombocytopenia, was recently shown [3] to be associated with severe thrombocytopathy (impairment of platelet aggregation, secretion and spreading due to inhibition of integrin alphaIIb betaIII). We report a type 2B VWD patient, diagnosed at the age of 8 years following investigations for severe epiCorrespondence: Eugenia Biguzzi, MD, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca’ Granda Maggiore Policlinico Hospital Foundation, via Pace 9, 20122 Milano, Italy. Tel.: +39 02 5503 5308; fax: +39 02 5503 5347; e-mail: [email protected] Accepted after revision 12 October 2014 DOI: 10.1111/hae.12580 Haemophilia (2015), 21, e70--e121
staxis. Laboratory parameters at diagnosis were as follows: bleeding time 100 50″, coagulant factor VIII (FVIII:C) 79%, VWF antigen (VWF:Ag) 64%, VWF Ristocetin cofactor activity (VWF:RCo) 22%, increased VWF ristocetin-induced platelet aggregation (VWF:RIPA), lack of high molecular weight VWF multimers, platelet count 146 9 109 L1, mutation p.R1308C. At the age of 37 years, the patient had an early foetal loss (9th week) and underwent revision of the uterine cavity, without any prophylaxis and no bleeding complications. At the age of 38 years, during her second pregnancy the patient received purified VWF concentrate (Wilfactin 25 U kg1 twice per week, from week 35 to week 37), albeit the absence of bleeding symptoms, because of severe thrombocytopenia (platelets 44 9 109 L1), that did not show any significant change after treatment (platelets ranging from 9 9 109 to 34 9 109 L1). At delivery (caesarean section at 38 weeks due to ‘unripe cervix for induction of labour’), the patient received one platelet transfusion (from HLA-matched single donor) with a good recovery of platelet number (65 9 109 L1, 1 h after transfusion), and Wilfactin 25 U kg1. FVIII:C and VWF:RCo were maintained between 100–147% and 70–100% respectively in the following 6 days (Wilfactin 12.5 U kg1 on day +3 and +6). VWF:RCo levels before and after treatment are shown in Fig. 1a. Haemoglobin level (13.5 g dL1 before surgery) decreased to 8.9 g dL1 and platelets count increased to 49 9 109 L1 at discharge from the hospital. Total consumption of Wilfactin was © 2014 John Wiley & Sons Ltd
LETTERS TO THE EDITORS (a1)
(b1)
2nd pregnancy: VWF:RCo
120
e99
3rd pregnancy: VWF:RCo
180
48 hs
160
100
140 120
%
%
80 60
100 80
40
60 40
20
20 0
0 35 week
36 week
37 week
cesarean day +3 section
Platelets
(a2)
31 week
35 week
cesarean section
Platelets
(b2)
70
60
60
50
50
40
x109/L
x10e3/mmc
33 week
40 30
30 20
20 10
10
0
0 35 week
36 week
37 week
cesarean day +3 section
31 week
33 week
35 week
cesarean section
Fig. 1. a1 and b1: VWF:RCo levels during 2nd and 3rd pregnancy. Vertical arrows indicate infusions of von Willebrand factor (VWF) concentrate (bolus), horizontal arrow indicates continuous infusion of VWF concentrate. a1 and b2: platelets values during 2nd and 3rd pregnancy. Arrows indicate platelet transfusions.
16 000 U (12 000 U before delivery, 2000 U before caesarean section and 2000 U in the postpartum period). A bleeding complication (subfascial haematoma) was ascertained 3 weeks after delivery, when the patient was evaluated by the obstetrician for pelvic pain; no surgical wound revision or substitutive therapy with VWF concentrate was necessary. A third pregnancy in 2013 (age 40 years), was characterized by thrombocytopenia: platelets 100 9 109 L1 at week 10, 46 9 109 L1 at week 19, 44 9 109 L1 at week 27. Because of low ferritin levels, albeit normal haemoglobin levels (Hb 12 g dL1), iron supplementation was started at 27 weeks. At 33 weeks, a mild increase in FVIII:C 91% and VWF:RCo 28% was associated with platelet count decrease (11 9 109 L1), associated with moderate gum bleeding that was treated with plasma-derived FVIII/VWF concentrate (Humate-P 25 FVIII U kg1). A blood film was performed showing platelet clumps and presence of giant platelets. For this reason, the platelet count was automatically repeated using the optical channel (49 9 109 L1). A second infusion of Humate-P (25 FVIII U kg1) was given at 35 weeks of gestation for gum bleeding again. In 36 + 4 week, haemoglobin was 13.6 g dL1, while © 2014 John Wiley & Sons Ltd
platelet count (automated optical method) dropped to 24 9 109 L1. A caesarean section was performed under general anaesthesia the following day. The patient was treated preoperatively with one platelet pool, intravenous tranexamic acid (1 g) and Humate-P (25 U FVIIII kg1). During surgery, continuous infusion of Humate-P was administrated (2 FVIII U kg1 h1). Good haemostatic control was observed during surgery, but subcutaneous oozing was noted at the end of surgery, with an estimated blood loss of 500 mL. Platelet count was evaluated 1 h after platelet pool administration, before the beginning of surgery, and showed no response to the transfusion (platelets before 32 9 109 L1, after 38 9 109 L1). FVIII:C and VWF:RCo were maintained above 100% for 48 h (progressive decrease and final stop of the continuous intravenous infusion). The patient received further treatments (Humate-P 25 FVIII U kg1) on days +4, +5, +7, +10. Total consumption of HumateP was 4000 U before delivery, 2000 U at caesarean section and 13 620 U after delivery. VWF:RCo levels before and after treatment are shown in Fig. 1b. Tranexamic acid was associated until day +7. Haemoglobin levels decreased for 13.6 g dL1 (prepartum) Haemophilia (2015), 21, e70--e121
e100
LETTERS TO THE EDITORS
Table 1. Data from the literature regarding pregnancy follow-up in patients affected by type 2B VWD. Patient – pregnancy
Author Rick et al. [4]
Casonato et al. [5]
1–2
2–2
Mutation
Age at delivery
Previous pregnancy with late foetal loss associated
Not reported
36
Planned caesarean section
Not reported
40 000
Not reported
Yes – number not reported
with hypertension Previous normal delivery
Not
33
Vaginal
Not reported
20 000 at delivery
Not reported
No
with mild bleeding 13 years ago Takafuta et al. [6]
Delivery
Delivery week
reported
Plt count/mmc
Anaesthesia
Prophylactic plt transfusion
Previous obstetrical history
(48 000 in day +2, 77 000 in day
3–1
p.R1308C
28
Caesarean section
42
+4) 130 000
Not reported
No
4–1
p.R1306W
26
Spontaneous vaginal
Not reported
72 000
Not reported
No
p.R1308C
34
Caesarean section
38
12 000
Not reported
No
26
Inducted vaginal delivery
36.5
17 000
Not reported
Yes – number not
(twin pregnancy) Vaginal
Not reported
Not reported
Not reported
reported No
Vaginal
39
25 000 (142 000 at
Notreported
Yes – 1 pool
5–2
Previous spontaneous delivery with important blood loss (1100 g) treated with transfusion (20 pool plt, 5 units
Foster [7]
6–1
fresh whole blood) Not reported
7–1
Not reported
7–2
Not reported
Burlingame et al.
8–1
[8] G€ uth et al., [9]
9–6
Not 5 vaginal delivery without bleeding complications, without prophylactic
reported Not
Not reported
reported
treatment 10 – 1
Not
30
reported
discharge)
Not reported Mathew et al. [10]
11 – 1
Not reported
Not reported
Not reported
Not eported
20 000
Not reported
No
Hepner et al. [11]
12 – 1
Not reported
33
Vaginal
39
20 000
None
No
35
Caesarean section
38
36 000
General
Yes – 1 pool without response +1 pool more
39
Labour induction, vaginal
39
31 000
Not reported
Yes – 1 pool with
12 – 2 pregnancy
De Wee et al., [12]
No data regarding
Ranger et al. [13]
deliveries in 15 patients 13 – 3 pregnancy
2 previous pregnancy
p.R1306W
losses at 7 weeks
14 – 1 pregnancy
delivery
p.R1306W
34
Urgent caesarean section
response (31 000 to >51 000) +6 more pools to maintain 38–39
126 000 (74 000 in
Spinal
plt counts >50 000 No
day +3)
14 – 2 pregnancy
15 – 3 pregnancy
2 previous deliveries with
p.R1306W
37
Elective caesarean section
39
48 000 (23 000 in day +1)
Not reported
Yes – 1 pool
p.R1308C
35
Caesarean section
38
278 000
General
No
p.P1337L
23
Vaginal
39
125 000
Epidural
No
p.R1308C
38
Caesarean section
38
27 000
General
Yes – 1 pool
p.R1308C
36 + 5
Caesarean section
38
32 000 (optical count)
General
Yes – 1 pool without response
important blood loss treated with transfusion and surgical intervention Lagarrigue et al.
16 – 1 pregnancy
[14]
Biguzzi et al., 2014
Not reported 17 – 2 pregnancy
Previous early foetal loss (9th week)
17 – 3 pregnancy
to 12.1 g dL1 (day +4 postpartum) and subsequently increased to 14.5 g dL1 (day +10 post partum). A progressive rise of platelet number was observed at day +4 (optical count 42 9 109 L1) and platelet count was 112 9 109 L1 at hospital discharge (day +10). No bleeding complications developed in the postpartum period. Antiembolism compression stockHaemophilia (2015), 21, e70--e121
ings were used during the first 5 days of the postpartum period. Ten case stories/series specifically reporting the management of type 2B VWD patients (n = 16) during pregnancy were published between 1987 and 2012 [4–13]. Table 1 summarizes patients’ characteristics and specific treatments. © 2014 John Wiley & Sons Ltd
LETTERS TO THE EDITORS
Prophylactic replacement therapy
Blood loss (mL)
Cryoprecipitate
1800
Fresh plasma before and
Not reported
Treatment: concentrate after delivery No
Transfusion/Other Not reported
Days of hospitalization
Total concentrate consumption for delivery
Readmission
Treatment during readmission
e101
DVT prophylaxis
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
after delivery
Humate-P 3000 U RCo
800
Haemate-P for 4
10 pool PLT
Not reported
Not reported
Not reported
Not reported
(42 U RCo kg1) No
1800
more days Haemate-P 4000 U RCo
Prostaglandin F2
Not reported
Haemate-P 4000 U
Not reported
Not reported
No
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Humate-P 2000 U RCo
700
(40 U Rco kg1) + 1000 U (20 U kg1)
Not specified FVIII concentrate 40–
(75 U RCo kg1) Haemate-P for 2 more days
No bleeding complications
60 U kg1
Not specified FVIII concentrate 40– 60 U kg1 for 7 days
No treatment
Bleeding complications
Multiple transfusions
Not reported
Not reported
Not reported
Not reported
No treatment
Bleeding complications
Multiple transfusions
Not reported
Not reported
Not reported
Not reported
Alphanate
Not reported
Not reported
Not reported
Not reported
No
No bleeding complications
Not reported
Not reported
Not reported
Humate-P
800 + 2000 (day +3)
3000 U + antifibrinolytic
Haemate-P
4 U RBC
Not reported
Haemate-P 5500 U
Not reported
1500 U + 1000 U dopo 6 ore Humate-P
No bleeding complications
Not reported
Humate-P 3000 U RCo (42 U kg1) – 1250 U
Not reported
Not reported
Not reported Humate-P 3000 U RCo (42 U kg1) – 1250 U
FVIII (18 U kg1) Humate-P 4200 U RCo – 1750 U FVIII
FVIII (18 U kg1) 1000
Humate-P 5000 U RCo every 12 h for
1 PLT pool
Yes – vaginal lacerations in day +5
Not reported Vaginal packing + RBC 4 units + Humate-P
Not reported
3000 U Rco + antifibrinolytic
Not reported
Humate-P 34 200 U Rco, 14 250 U FVIII
Not reported
Not reported
3 (80 000 plt at discarge)
Not reported
Not reported
Antiembolism
3 days
Regular infusion of
Not clinically significant
Humate-P
Desmopressin
compression stocking
500
Yes – pelvic pain
Not reported
Antibiotics only
Not reported
Surgical revision and haemostatic treatment
Antiembolism compression stocking
(presumed infected muscular haematoma) in day +10 Humate-P 25 U FVIII kg1
1000
Humate-P 30 U kg1 FVIII
900 (significant generalizedoozing at surgery)
Wilfactin 4000 U
