TABLE 2

Common Testing Strategies for Bleeding Disorders

ConditionFrequencyInheritanceScreening TestsSn and Sp, %PPV and NPV,%Confirmatory Test
Factor abnormalities/deficiencies
 VWD type 11/1000ADPFA-100Sn = 79–96aPPV = 93.3VWAgb
VWF activity
Sp = 88–96aNPV = 98.2VW multimer analysis
Factor VIII activity
 VWD type 2AUncommonAD or ARPFA-100Sn = 94–100aPPV = 93.3VWAgb
VWF activity
Sp = 88–96aNPV = 98.2VW multimer analysis
Factor VIII activity
 VWD type 2BUncommonADPFA-100Sn = 93–96aPPV = 93.3VWAgb
VWF activity
Sp = 88–96aNPV = 98.2VW multimer analysis
Factor VIII activity
 VWD type 2MUncommonAD or ARPFA-100Sn = 94–97aPPV = 93.3VWAgb
VWF activity
Sp = 88–96aNPV = 98.2VW multimer analysis
Factor VIII activity
 VWD type 2NUncommonAR, or compound heterozygoteaPTTNANAVWF-Factor VIII binding assay
 VWD type 31/300 000–1 000 000AR, or compound heterozygotePFA-100Sn = 94–100aPPV = 93.3VWAgb
Ristocetin cofactor
Sp = 88–96aNPV = 98.2VWF multimer analysis
Factor VIII activity
 Factor II deficiency (prothrombin)26 reported cases, estimated 1/1–2 millionaPTT, PT (may be normal)Sn = variableNAFactor II activity ± antigen levels
 Factor V deficiency1/1 millionARaPTT, PTSn = variableNAFactor V activity
 Combined Factor V/Factor VIII deficiency1/1 millionARaPTT>PTSn = variableNAFactor V and factor VIII activities
 Factor VII deficiency1/300 000–500 000ARPTSn = variableNAFactor VII activity
 Factor VIII deficiency1/5000 male birthsX-linkedaPTTSn = variableNAFactor VIII activity
 Factor IX deficiency1/20 000 male birthsX-linkedaPTTSn = variableNAFactor IX activity
 Factor X deficiency1/1 millionARaPTT, PT, RVVSn = variableNAFactor X activity
 Factor XI deficiency1/100 000ARaPTTSn = variableNAFactor XI activity
 Factor XIII deficiency1/2–5 millionARClot solubilitySn = variableNAFactor XIII activity
Fibrinolytic defects
 α-2 antiplasmin deficiency∼40 reported casesAREuglobin lysis testSn = variableNAα-2 antiplasmin activity
 PAI-1 deficiencyVery rareARSn = variableNAPAI -1 antigen and activity
Defects of fibrinogen
 Afibrinogenemia1/500 000ARPT, aPTTSn = highNAFibrinogen level
 HypofibrinogenemiaLess than afibrinogenemiaPT, aPTTSn = variableNAThrombin time, fibrinogen activity
 Dysfibrinogenemia1/millionThrombin time, fibrinogen levelSn = variableNAThrombin time, fibrinogen antigen and activity level comparison, reptilase time
Platelet disorders
 ITPAge-relatedNACBCSn = highNAAntiplatelet Ab (rarely needed)
 Glanzmann thrombastheniaVery rareARPFA-100Sn = 97–100NAPlatelet aggregation testing Flow cytometry
 Bernard Soulier syndromeRareARPFA-100Sn = 100NAPlatelet aggregation testing Flow cytometry
 Platelet release/storage disordersUnknown, more common than other platelet function disordersvariablePFA-100Sn = 27–50NAPlatelet aggregation and secretion
Electron microscopy
Molecular and cytogenetic testing
  • AD, autosomal dominant; AR, autosomal recessive; CBC, complete blood cell (count); NA, not available or not applicable; NPV, negative predictive value; PAI-1, plasminogen activator inhibitor-1; PPV, positive predictive value; RVV, Russell viper venom (test); Sn, sensitivity; Sp, specificity; VW, von Willebrand; VWAg, von Willebrand antigen; VWF, von Willebrand factor Ab, antibody.

  • a Values derived from data before 2008 National Institutes of Health Consensus guidelines. Sn and Sp using current diagnostic cutoffs unknown but would be expected to have higher Sp with lower Sn.

  • b May be reasonable to proceed directly to diagnostic testing depending on availability. See accompanying technical report for detailed discussion.24