Diagnosis Von Willebrand disease

1 diagnosis

1.1 types

1.1.1 type 1
1.1.2 type 2

1.1.2.1 type 2a
1.1.2.2 type 2b
1.1.2.3 type 2m
1.1.2.4 type 2n (normandy)


1.1.3 type 3
1.1.4 platelet-type
1.1.5 acquired

diagnosis

when vwd suspected, blood plasma of patient must investigated quantitative , qualitative deficiencies of vwf. achieved measuring amount of vwf in vwf antigen assay , functionality of vwf glycoprotein (gp)ib binding assay, collagen binding assay, or ristocetin cofactor activity (ricof) or ristocetin induced platelet agglutination (ripa) assays. factor viii levels performed because factor viii bound vwf protects factor viii rapid breakdown within blood. deficiency of vwf can lead reduction in factor viii levels, explains elevation in ptt. normal levels not exclude forms of vwd, particularly type 2, may revealed investigating platelet interaction subendothelium under flow, highly specialized coagulation study not routinely performed in medical laboratories. platelet aggregation assay show abnormal response ristocetin normal responses other agonists used. platelet function assay may give abnormal collagen/epinephrine closure time, , in cases, normal collagen/adp time. type 2n may considered if factor viii levels disproportionately low, confirmation requires factor viii binding assay. additional laboratory tests classify sub-types of vwd include von-willebrand multimer analysis, modified ristocetin induced platelet aggregation assay , vwf propeptide vwf antigen ratio propeptide. in cases of suspected acquired von-willebrand syndrome, mixing study study (analysis of patient plasma along pooled normal plasma/pnp , mixture of 2 tested immediately, @ 1 hour, , @ 2 hours) should performed. detection of vwd complicated vwf being acute phase reactant levels rising in infection, pregnancy, , stress.

other tests performed in patient bleeding problems complete blood count-cbc (especially platelet counts), activated partial thromboplastin time-aptt, prothrombin time international normalized ratio-ptinr, thrombin time-tt, , fibrinogen level. testing factor ix may performed if hemophilia b suspected. other coagulation factor assays may performed depending on results of coagulation screen. patients von willebrand disease typically display normal prothrombin time , variable prolongation of partial thromboplastin time.

the testing vwd can influenced laboratory procedures. numerous variables exist in testing procedure may affect validity of test results , may result in missed or erroneous diagnosis. chance of procedural errors typically greatest during preanalytical phase (during collecting storage , transportation of specimen) when testing contracted outside facility , specimen frozen , transported long distances. diagnostic errors not uncommon, , rate of testing proficiency varies amongst laboratories, error rates ranging 7 22% in studies high 60% in cases of misclassification of vwd subtype. increase probability of proper diagnosis, testing should done @ facility immediate on-site processing in specialized coagulation laboratory.

types

the 4 hereditary types of vwd described type 1, type 2, type 3, , pseudo- or platelet-type. cases hereditary, acquired forms of vwd have been described. international society on thrombosis , haemostasis s classification depends on definition of qualitative , quantitative defects.

von willebrand disease type iii (and ii) inherited in autosomal recessive pattern.


type 1

type 1 vwd (60-80% of vwd cases) quantitative defect heterozygous defective gene. can arise failure secrete vwf circulation or vwf being cleared more normal. decreased levels of vwf detected @ 20-50% of normal, i.e. 20-50 iu.

many patients asymptomatic or may have mild symptoms , not have impaired clotting, might suggest bleeding disorder. often, discovery of vwd occurs incidentally other medical procedures requiring blood work-up. cases of type 1 vwd never diagnosed due asymptomatic or mild presentation of type , people end leading normal life free of complications, many being unaware have disorder.

trouble may, however, arise in patients in form of bleeding following surgery (including dental procedures), noticeable easy bruising, or menorrhagia (heavy menstrual periods). minority of cases of type 1 may present severe hemorrhagic symptoms.

type 2

type 2 vwd (15-30% of cases) qualitative defect , bleeding tendency can vary between individuals. 4 subtypes exist: 2a, 2b, 2m, , 2n. these subtypes depend on presence , behavior of underlying multimers.

type 2a

the vwf quantitatively normal qualitatively defective. ability of defective von willebrand factors coalesce , form large vwf multimers impaired, resulting in decreased quantity of large vwf multimers , low rcof activity. small multimer units detected in circulation. von willebrand factor antigen (vwf:ag) assay low or normal.

type 2b

this gain of function defect. ability of qualitatively defective vwf bind glycoprotein ib (gpib) receptor on platelet membrane abnormally enhanced, leading spontaneous binding platelets , subsequent rapid clearance of bound platelets , of large vwf multimers. thrombocytopenia may occur. large vwf multimers reduced or absent circulation.

the ristocetin cofactor activity low when patient s platelet-poor plasma assayed against formalin-fixed, normal donor platelets. however, when assay performed patient s own platelets (platelet-rich plasma), lower-than-normal amount of ristocetin causes aggregation occur. due large vwf multimers remaining bound patient s platelets. patients subtype unable use desmopressin treatment bleeding, because can lead unwanted platelet aggregation , aggravation of thrombocytopenia.

type 2m

type 2m vwd qualitative defect of vwf characterized decreased ability bind gpib receptor on platelet membrane , normal capability @ multimerization. vwf antigen levels normal. ristocetin cofactor activity decreased , high molecular weight large vwf multimers present in circulation.

type 2n (normandy)

this deficiency of binding of vwf coagulation factor viii. vwf antigen test normal, indicating normal quantity of vwf. ristocetin cofactor assay normal. assay coagulation factor viii revealed marked quantitative decrease equivalent levels seen in hemophilia a. has led vwd type 2n patients being misdiagnosed having hemophilia a.

type 3

type 3 severe form of vwd (homozygous defective gene) , characterized complete absence of production of vwf. von willebrand factor undetectable in vwf antigen assay. since vwf protects coagulation factor viii proteolytic degradation, total absence of vwf leads extremely low factor viii level, equivalent seen in severe hemophilia clinical manifestations of life-threatening external , internal hemorrhages. inheritance pattern of vwd type 3 autosomal recessive, while inheritance pattern of hemophilia x-linked recessive.

platelet-type

platelet-type vwd (also known pseudo-vwd) autosomal dominant genetic defect of platelets. vwf qualitatively normal , genetic testing of von willebrand gene , vwf protein reveals no mutational alteration. defect lies in qualitatively altered gpib receptor on platelet membrane increases affinity bind vwf. large platelet aggregates , high molecular weight vwf multimers removed circulation resulting in thrombocytopenia , diminished or absent large vwf multimers. ristocetin cofactor activity , loss of large vwf multimers similar vwd type 2b.

acquired

acquired vwd can occur in patients autoantibodies. in case, function of vwf not inhibited, vwf-antibody complex rapidly cleared circulation.

a form of vwd occurs in patients aortic valve stenosis, leading gastrointestinal bleeding (heyde s syndrome). form of acquired vwd may more prevalent presently thought. in 2003, vincentelli et al. noted patients acquired vwd , aortic stenosis underwent valve replacement experienced correction of hemostatic abnormalities, hemostatic abnormalities can recur after 6 months when prosthetic valve poor match patient. similarly, acquired vwd contributes bleeding tendency in people implant of left ventricular assist device (a pump pumps blood left ventricle of heart aorta). large multimers of vwf destroyed mechanical stress in both conditions.

thrombocythemia cause of acquired von willebrand disease, due sequestration of vwf via adhesion of vast numbers of platelets. acquired vwd has been described in wilms tumour, hypothyroidism, , placental mesenchymal dysplasias.