Laboratory evaluation for suspected familial or acquired thrombophilia (tests are suggested and should be performed selectively based on clinical judgment; see text).
Initial General Diagnostic and Special Coagulation Laboratory Testing |
CBC with peripheral smear |
Prothrombin time |
Activated partial thromboplastin time (aPTT; using a thromboplastin that is relatively sensitive to the presence of a lupus anticoagulant) |
Thrombin time and reptilase time (to detect a heparin or direct thrombin inhibitor effect, and to screen for dysfibrinogenemia) |
Lupus anticoagulant panel (to include at least two phospholipid-dependent clot-based assays that interrogate at least two of either the intrinsic [sensitive aPTT, Kaolin Clot Time], extrinsic [dilute prothrombin time] or common [dilute Russell viper venom time, Ecarin or Textarin clotting times] procoagulant pathways, along with mixing studies to show inhibition and “confirm” studies [e.g., platelet neutralization procedure, hexagonal phase phospholipid] to show phospholipid-dependent inhibition) |
Anticardiolipin and anti-β2 glycoprotein 1 antibodies (IgG and IgM isotypes) |
Activated Protein C (APC)–resistance ratio (second generation; “factor V–deficient plasma” mixing study) |
Fibrinogen, soluble fibrin monomer complex and quantitative plasma fibrin D-dimer (to screen for intravascular coagulation and fibrinolysis [DIC]). |
Prothrombin G20210GA mutation genotyping (direct genomic DNA mutation testing) |
Plasma homocysteine (basal) |
Additional Selective Special Coagulation Laboratory Testing |
Factor V Leiden mutation genotyping (if the APC-resistance ratio is abnormal [low]; direct genomic DNA mutation testing) |
For patients with idiopathic or recurrent venous thromboembolism; a first episode of venous thromboembolism at a “young” age; a family history of venous thromboembolism; venous thrombosis in an unusual vascular territory; neonatal purpura fulminans or warfarin-induced skin necrosis: |
-antithrombin activity (followed by antithrombin antigen level if the activity is low) |
-protein C activity (followed by protein C antigen level if the activity is low) |
-protein S activity (followed by free protein S antigen level if the activity is low. The total protein S antigen level may be helpful if the free protein S antigen is low) |
Flow cytometry for paroxysmal noctural hemoglobinuria |
Plasma ADAMTS-13 activity (for acquired or familial thrombotic thrombocytopenic purpura) |
Plasminogen activity (for ligneous conjunctivitis/gingivitis) |
Heparin-induced thrombocytopenia testing (plasma anti-PF4/glycosaminoglycan antibodies [ELISA]; platelet 14C-serotonin release assay; heparin-dependent platelet aggregation) |
Quantitative PCR assay for JAK2 mutation (for splanchnic or portal vein thrombosis). |
Additional Selective General Diagnostic Testing |
ESR, chemistries, PSA, β-HCG, Ca-125, ANA, (dsDNA, RF, ENA) |
PA/lateral CXR, urinalysis, mammogram |
Colon imaging, especially if no prior screening (proctosigmoidoscopy, colonoscopy) |
Chest imaging for smokers (CT, MRI) |
ENT consultation, especially for smokers |
UGI/upper endoscopy |
Abdominal imaging (CT) |
Endometrial biopsy if endometrial cancer suspected |
Angiography |
Initial General Diagnostic and Special Coagulation Laboratory Testing |
CBC with peripheral smear |
Prothrombin time |
Activated partial thromboplastin time (aPTT; using a thromboplastin that is relatively sensitive to the presence of a lupus anticoagulant) |
Thrombin time and reptilase time (to detect a heparin or direct thrombin inhibitor effect, and to screen for dysfibrinogenemia) |
Lupus anticoagulant panel (to include at least two phospholipid-dependent clot-based assays that interrogate at least two of either the intrinsic [sensitive aPTT, Kaolin Clot Time], extrinsic [dilute prothrombin time] or common [dilute Russell viper venom time, Ecarin or Textarin clotting times] procoagulant pathways, along with mixing studies to show inhibition and “confirm” studies [e.g., platelet neutralization procedure, hexagonal phase phospholipid] to show phospholipid-dependent inhibition) |
Anticardiolipin and anti-β2 glycoprotein 1 antibodies (IgG and IgM isotypes) |
Activated Protein C (APC)–resistance ratio (second generation; “factor V–deficient plasma” mixing study) |
Fibrinogen, soluble fibrin monomer complex and quantitative plasma fibrin D-dimer (to screen for intravascular coagulation and fibrinolysis [DIC]). |
Prothrombin G20210GA mutation genotyping (direct genomic DNA mutation testing) |
Plasma homocysteine (basal) |
Additional Selective Special Coagulation Laboratory Testing |
Factor V Leiden mutation genotyping (if the APC-resistance ratio is abnormal [low]; direct genomic DNA mutation testing) |
For patients with idiopathic or recurrent venous thromboembolism; a first episode of venous thromboembolism at a “young” age; a family history of venous thromboembolism; venous thrombosis in an unusual vascular territory; neonatal purpura fulminans or warfarin-induced skin necrosis: |
-antithrombin activity (followed by antithrombin antigen level if the activity is low) |
-protein C activity (followed by protein C antigen level if the activity is low) |
-protein S activity (followed by free protein S antigen level if the activity is low. The total protein S antigen level may be helpful if the free protein S antigen is low) |
Flow cytometry for paroxysmal noctural hemoglobinuria |
Plasma ADAMTS-13 activity (for acquired or familial thrombotic thrombocytopenic purpura) |
Plasminogen activity (for ligneous conjunctivitis/gingivitis) |
Heparin-induced thrombocytopenia testing (plasma anti-PF4/glycosaminoglycan antibodies [ELISA]; platelet 14C-serotonin release assay; heparin-dependent platelet aggregation) |
Quantitative PCR assay for JAK2 mutation (for splanchnic or portal vein thrombosis). |
Additional Selective General Diagnostic Testing |
ESR, chemistries, PSA, β-HCG, Ca-125, ANA, (dsDNA, RF, ENA) |
PA/lateral CXR, urinalysis, mammogram |
Colon imaging, especially if no prior screening (proctosigmoidoscopy, colonoscopy) |
Chest imaging for smokers (CT, MRI) |
ENT consultation, especially for smokers |
UGI/upper endoscopy |
Abdominal imaging (CT) |
Endometrial biopsy if endometrial cancer suspected |
Angiography |