Vwd Pocket Guide

8/6/2019 Vwd Pocket Guide

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von Willebrand DiseaseThe Diagnosis, Evaluation, and Management of

National Heart, Lung, and Blood Institute VWD Exper

A P O C K E T G U I D E T O

NIH Publication No. 08-5833February 2008


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Questions to Patient History From Patient

1) Have you or a blood relative ever needed medical attention fora bleeding problem, or been told you have a bleeding disorder orproblem: During /after surgery? With dental procedures, extractions? With trauma? During childbirth or for heavy menses? Ever had bruises with lumps?

2) Do you have or have you ever had: Liver or kidney disease; a blood or bone

marrow disorder; a high or low platelet count?3) Do you take aspirin, NSAIDs (provide common names), clopidogrel

(PlavixTM), warfarin, heparin?

No evaluation; usual care

No further evaluation;usual care

Evaluate further: initiallaboratory tests andpossible referral (SeeFigure 2.)

Ask additional questions (seeBox 1) and the 3 questions above(if not already asked) AND obtainhistory of treatment (e.g., bloodtransfusion). Examine for bleed-ing or underlying disease.

Personal history of VWD

Abnormal laboratory test

Positive family history of ableeding disorder or bleeding

Patient is concerned aboutbleeding; patient who hasunexplained anemia or historyof previous DDAVP use

Negative Positive

No Yes

Figure 1:Initial Evaluation for VWD or other Bleeding Disorders

(e.g., an asymptomatic patient who will undergo surgery or other interventional procedure)1. Do you have a blood relative who has a

bleeding disorder, such as von Willebranddisease or hemophilia?

2. Have you ever had prolonged bleeding fromtrivial wounds, lasting more than 15 minuteor recurring spontaneously during the7 days after the wound?

3. Have you ever had heavy, prolonged, orrecurrent bleeding after surgical proceduressuch as tonsillectomy?

4. Have you ever had bruising, with minimalor no apparent trauma, especially if youcould feel a lump under the bruise?

5. Have you ever had a spontaneous nose-bleed that required more than 10 minutesto stop or needed medical attention?

6. Have you ever had heavy, prolonged, orrecurrent bleeding after dental extractionsthat required medical attention?

7. Have you ever had blood in your stool, uneplained by a specific anatomic lesion (such

as an ulcer in the stomach, or a polyp in thecolon), that required medical attention?8. Have you ever had anemia requiring

treatment or received a blood transfusion?9. For women, have you ever had heavy

menses, characterized by the presence ofclots greater than an inch in diameterand/or changing a pad or tampon morethan hourly, or resulting in anemia or lowiron level?

Box 1: Additional Questions To Screenfor a Bleeding Disorder

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Initial Evaluation(history and physical

examination) (See Figure 1.)

Positive Negative

Possible referral for otherappropriate evaluation

1 or more testsabnormal

Referral for otherappropriate evaluation

Other cause identified, e.g.,platelets*, isolated abnormal

PT, low fibrinogen, abnormal TT

No further evaluation

Laboratory Evaluation

Initial hemostasis tests CBC and platelet count PTT PT Fibrinogen or TT (optional)

If bleeding history is strong,consider performing initial

VWD assays

Isolated prolonged PTT thatcorrects on 1:1 mixing study,

or no abnormalities

Referral for selected specializedVWD studies

Repeat initial VWD assays ifnecessary

Ratio of VWF:RCo to VWF:Ag Multimer distribution Collagen binding RIPA or platelet binding FVIII binding Platelet VWF studies DNA sequencing of VWF gene

Figure 2. Laboratory Assessment for VWD or other Bleeding Disorders

* Isolated decreased platelets mayoccur in VWD type 2B.

+ Correction in the PTT mixing studyimmediately and after 2-hourincubation removes a factor VIII(FVIII) inhibitor from consideration.Investigation of other intrinsic factorsand lupus anticoagulant also may beindicated.

CBC = complete blood count;PT=prothrombin time; PTT = partialthromboplastin time; RIPA = Ristocetin-induced platelet aggregation;TT = thrombin time; WVF:Ag = VWFantigen; VWF:RCo = VWF Ristocetincofactor activity. Referral to ahemostasis specialist is appropriate forhelp in interpretation, repeat testing,and specialized tests.

See full guidelines for levels ofevidence for each recommendationwww.nhlbi.nih.gov/guidelines/vwd

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Initial VWD assays VWF:Ag VWF:RCo FVIII

No test abnormal


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MAKING THE DIAGNOSIS OF VWD

Condition

Type 1

Type 2A

Type 2B

Type 2M

Type 2N

Type 3

Low VWF**Normal

VWF:RCo(IU/dL)


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M A N A G E M E N T O F V W D

Treatment is aimed at cessation of bleeding orprophylaxis for surgical procedures. Strategiesinclude:

increasing plasma concentration of VWF by releasing endogenous VWF stores throughstimulation of endothelial cells with DDAVP.

replacing VWF by using human plasma-derived,viral-inactivated concentrates.

using agents that promote hemostasis and wound healing but do not substantially alterthe plasma concentration of VWF.

These strategies are not mutually exclusive, andpatients may receive any one or all three at thesame time. The appropriate therapy depends onthe type and severity of VWD, the severity of thehemostatic challenge, and the nature of the actualor potential bleeding.

Note: the following recommendations are gradedaccording to level of evidence. See full guidelinesfor further explanation and evidence tables.(www.nhlbi.nih.gov/guidelines/vwd)

Testing Prior to Treatme nt

A. Before treatment (except in urgent situations),persons suspected of having VWD should havea laboratory-confirmed diagnosis. (C, IV)

B. Persons without a definite diagnosis of VWDbut with VWF:RCo levels of 3050 IU/dL and ableeding history may benefit from treatment orprophylaxis of bleeding in certain clinicalsituations. (B, III)

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C. Persons with VWF:RCo >10 IU/dL and FVIIIactivity >20 IU/dL should undergo a trial of DDAVP while in a nonbleeding state. Personswith levels below these thresholds are less likely to respond usefully to DDAVP, but a DDAVPtrial should still be considered. (B, IIa)

General Management of VWD PatientsA. Treatment is aimed at cessation of bleeding or

surgical prophylaxis. (C, IV)

B. Continued bleeding, despite adequately replaced VWF:RCo and FVIII activity levels,requires evaluation for other causes of bleeding. (C, IV)

C. Long-term prophylaxis is rarely required; it iscurrently under investigation. (C, IV)

D. Patients > 2 years of age should be immunizedagainst hepatitis A and B. (C, IV)

E. Patients should have the opportunity to talk toa knowledgeable genetic counselor. (C, IV)

F. Counsel patients to avoid aspirin, otherNSAIDs, and other platelet-inhibiting drugs.(C, IV)

G. Restriction of fluids to maintenance levelsshould be considered in persons receivingDDAVP (especially young children and insurgical settings) to avoid hyponatremia andseizures. (C, IV)

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eatment of Minor Bleeding and Prophylaxis forMinor Sur

gery

A. Epistaxis and oropharyngeal, soft tissue, orminor bleeding should be treated with


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intravenous or nasal DDAVP, if supported by results of a DDAVP trial. (B, IIa)

B. If elevation of VWF is necessary and responseto DDAVP is inadequate, VWF concentrateshould be used, with dosing primarily based onVWF:RCo units and secondarily on FVIII units.

(C, IV)C. For minor surgery, initial prophylactic

treatment should achieve VWF:RCo and FVIIIactivity levels 30 IU/dL and preferably >50IU/dL, and should be maintained for 1-5 days.(B, III)

D. Management of minor bleeding (e.g., epistaxis,simple dental extraction, or menorrhagia) withDDAVP and proper fluid restriction can be

performed without monitoring of electrolytesunless Stimate or DDAVP is used more thanthree times within 72 hours. (C, IV)

E. For persons with mild to moderate VWD,antifibrinolytics combined with DDAVP aregenerally effective for oral surgery. VWFconcentrate should be available for persons whocannot receive DDAVP or who bleedexcessively despite this combined therapy.(B, IIb)

F. Topical agents, such as fibrin sealant or bovinethrombin, may be useful adjuncts for oralsurgery. Careful attention to hemostasis of atooth extraction socket and to suturing of sockets is also important. (C, IV)

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eatment of Major Bleeding and Prophylaxis forMajor Sur

gery

A. All treatment plans should be based onobjective laboratory determination of responseof VWF:RCo and FVIII activity levels toDDAVP or to VWF concentrate infusion.

(B, IIb)B. Whenever possible, all major surgeries and

bleeding events should be treated in hospitalswith a 24-hour/day laboratory and with clinicalmonitoring by a team including a hematologistand a surgeon skilled in the management of bleeding disorders. (C, IV)

C. For severe bleeding (e.g., intracranial, retroperi-toneal) or prophylaxis of major surgery, initial

target VWF:RCo and FVIII activity levelsshould be 100 IU/dL. Subsequent dosingshould maintain VWF:RCo and FVIII levelsabove a trough of 50 IU/dL for at least 710days. (B, III)

D. To decrease risk of perioperative thrombosis,VWF:RCo levels should not exceed 200 IU/dL,and FVIII activity should not exceed 250IU/dL. (C, IV)

E. For major surgical procedures in selectedpatients with type 3 VWD or AVWS who areat risk for poor VWF recovery because of inhibitors, a preoperative trial infusion of VWFconcentrate with pharmacokinetic laboratory monitoring should be considered. (C, IV)


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for prenatal care, delivery, termination of pregnancy, or management of miscarriage.(C, IV)

2. administer prophylaxis with DDAVP orVWF concentrate before invasiveprocedures. (C, IV)

3. achieve VWF:RCo and FVIII levels of atleast 50 IU/dL before delivery and maintainthose levels for at least 35 days afterward.(C, IV)

C. If VWF:RCo and FVIII levels can be monitoredand maintained above 50 IU/dL during laborand delivery, and no other coagulation defectsare present, then regional anesthesia may beconsidered. (C, IV)

D. Because coagulation factors return toprepregnancy levels within 1421 days afterdelivery, health care providers should be inclose contact with women during thepostpartum period. (C, IV)

Acquired von Willebrand Syn drome (AVWS)

A. AVWS patients who require surgery should beconsidered for a pharmacokinetic trial of

therapy with DDAVP and/or VWF concentrate,with monitoring of VWF:RCo and FVIII levels,to evaluate for possible accelerated clearance of VWF. (C, IV)

B. For AVWS patients who bleed excessively despite therapy with DDAVP and VWFconcentrate, treatment with high-dose IGIVshould be considered, especially in IgG isotypeMGUS. (B, IIa)

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Management of Menorrhagia and HemorrhagicOvarian Cysts

A. Women with menorrhagia or abnormal vaginalbleeding should have a full gynecologicalevaluation before therapy. (C, IV)

B. In the adolescent or adult woman who does notdesire pregnancy, but may desire future child-bearing, the first choice of therapy for eithermenorrhagia or to prevent hemorrhagicovarian cysts should be combined oralcontraceptives. (B, III and C, IV, respectively)

C. If a woman would otherwise be a suitablecandidate for an intrauterine device, the secondchoice of therapy for menorrhagia should bethe levonorgestrel intrauterine system. (B, IIb)

D. For the woman who desires pregnancy, DDAVP,antifibrinolytics, or VWF concentrate may betried to control menorrhagia. (C, IV)

E. Dilation and curettage is not usually effective tomanage excessive uterine bleeding in womenwho have VWD. (C, IV)

Management of Pregnancy and Childbirth

A. Women planning for pregnancy shouldhave, before conception, an evaluation by ahematologist and a high-risk obstetrician whoare skilled in the management of VWD. (C, IV)

B. For women who have type 1, type 2, or type 3VWD, with FVIII or VWF:RCo levels


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For More Information

The NHLBI Health Information Center is a service of the National Heart,Lung, and Blood Institute (NHLBI) of the National Institutes of Health.The NHLBI Health Information Center provides information to healthprofessionals, patients, and the public about the treatment, diagnosisand prevention of heart, lung, and blood diseases and sleep disorders.For more information, contact:

NHLBI Health Information CenterP.O. Box 30105Bethesda, MD 20824-0105Phone: 301-592-8573TTY: 240-629-3255Fax: 301-592-8563Web site: http://www.nhlbi.nih.gov

Copies of this and other publications are available in bulk at discountedrates.

Copies of the full VWD Guidelines report, as well as this Pocket Guide anda patient education brochure (In Brief: Your Guide to von WillebrandDisease) are available on the NHLBI Web site and from the NHLBI HealthInformation Center.

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DISCRIMINATION PROHIBITED: Under provisions of applicable public lawsenacted by Congress since 1964, no person in the United States shall, onthe grounds of race, color, national origin, handicap, or age, be excludedfrom participation in, be denied the benefits of, or be subjected todiscrimination under any program or activity (or, on the basis of sex, withrespect to any education program or activity) receiving Federal financialassistance. In addition, Executive Order 11141 prohibits discriminationon the basis of age by contractors and subcontractors in the performance

of Federal contracts, and Executive Order 11246 states that no federallyfunded contractor may discriminate against any employee or applicantfor employment because of race, color, religion, sex, or national origin.Therefore, the National Heart, Lung, and Blood Institute must be operatedin compliance with these laws and Executive Orders.

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Vwd Pocket Guide