Skip to content
SearchProgress
Display

Display

Theme
Density
Text size

Sign in

Add your earlier progress to your account?

Study progress is waiting to be saved

Von Willebrand, HIT, DIC and anticoagulant assays

15 min

  • Classify a von Willebrand panel from antigen, activity ratio, and factor VIII
  • Sequence HIT immunoassay and functional testing by pretest probability
  • Recognize the platelet, PT, D-dimer, and fibrinogen changes that suggest DIC
  • Choose the calibrated assay that measures a stated heparin or direct oral anticoagulant

Read the full reference

Try first

Try first

A von Willebrand factor (VWF) panel shows VWF antigen 55 IU/dL and platelet-dependent VWF activity 30 IU/dL, an activity-to-antigen ratio of 0.55. Factor VIII activity is 48 IU/dL. What does this ratio support?

The next section explains it.

Right. The next section explains why.

The next section explains it.

The next section explains it.

Get the idea

Classifying a VWF panel

The initial VWD panel combines VWF antigen, platelet-dependent VWF activity, and factor VIII activity. An activity-to-antigen ratio below 0.7 supports a qualitative type 2 defect. A ratio at or above 0.7, with both values proportionately reduced, fits type 1. Multimer analysis or collagen-binding activity then separates the type 2 subtypes.1

HIT testing follows pretest probability

The 4Ts score weighs thrombocytopenia depth, timing after heparin exposure, thrombosis, and competing causes. With an intermediate or high score, a PF4-heparin immunoassay screens first. A positive immunoassay shows binding antibody. A functional assay, such as the serotonin-release assay, shows activation at a low heparin concentration that saturating heparin suppresses, and that heparin-dependent pattern is what confirms heparin-induced thrombocytopenia (HIT).2

DIC is read from the whole pattern

Disseminated intravascular coagulation (DIC) needs a compatible trigger together with falling platelets, a lengthening prothrombin time (PT), a raised D-dimer, and falling fibrinogen. The 2025 International Society on Thrombosis and Haemostasis (ISTH) score scales each component against the assay's own D-dimer upper limit of normal, and a total of 5 or more is compatible with overt DIC in the right setting.3 A single raised D-dimer, without the trigger and the other changes, overcalls DIC.

Matching the anticoagulant to its assay

Anti-Xa results are quantitative only against the drug's own calibrator. A heparin-calibrated anti-Xa assay falsely raises a result for apixaban or rivaroxaban, and neither the PT nor the APTT can quantify either drug.4 A drug-calibrated anti-Xa assay measures direct factor Xa inhibitors, and a dilute thrombin time or an ecarin-based assay measures dabigatran.

References
  1. James PD, Connell NT, Ameer B, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021;5(1):280-300. doi:10.1182/bloodadvances.2020003265
  2. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392. doi:10.1182/bloodadvances.2018024489
  3. Iba T, Levy JH, Maier CL, et al. Updated definition and scoring of disseminated intravascular coagulation in 2025: communication from the ISTH SSC Subcommittee on Disseminated Intravascular Coagulation. J Thromb Haemost. 2025;23(7):2356-2362. doi:10.1016/j.jtha.2025.03.038
  4. Douxfils J, Adcock DM, Bates SM, et al. 2021 update of the International Council for Standardization in Haematology recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2021;121(8):1008-1020. doi:10.1055/a-1450-8178

Watch one

A patient's platelet count has fallen more than 50% from baseline, with a nadir of 35 × 10³/µL, beginning 7 days after starting unfractionated heparin for a different indication. No other cause of thrombocytopenia is apparent.

  1. Score the 4Ts: a fall greater than 50% with this nadir, this timing, and no competing cause gives an intermediate or high score.

    The 4Ts score weighs exactly these features and sets the pretest probability before any testing begins.

  2. Decide to test, since the score is intermediate or high.

    Testing at a low pretest probability risks a false-positive antibody result being treated as HIT, so the score decides whether to test at all.

  3. Order the PF4-heparin immunoassay first.

    The immunoassay is broad and sensitive, a reasonable first test, but it detects binding antibody whether or not that antibody activates platelets.

  4. If the immunoassay is positive, order a functional assay, such as the serotonin-release assay, before treating the result as confirmed HIT.

    Only a functional assay shows the heparin-dependent activation pattern that separates a platelet-activating antibody from one that is not.

Test in this order: the PF4-heparin immunoassay first, then a functional assay to confirm platelet activation, because the pretest probability from the 4Ts score supports testing at all.

Your turn

Problem 1 of 3

In a patient with sepsis, platelets are 40 × 10³/µL, D-dimer is 5 times the assay's upper limit of normal (ULN), PT is 4 seconds above control, and fibrinogen is 120 mg/dL. What is the 2025 ISTH disseminated intravascular coagulation (DIC) score, and what does it mean?

Incorrect. A total of 4 comes from scoring the platelet count of 40 × 10³/µL as 1 point. A count below 50 × 10³/µL scores 2.

Correct. Platelets below 50 × 10³/µL score 2, D-dimer above 3 to 7 × ULN scores 2, a PT prolongation of 3 to below 6 seconds scores 1, and fibrinogen of 100 mg/dL or higher scores 0. Sepsis supplies the compatible trigger the score requires.

Incorrect. Fibrinogen scores 1 point only below 100 mg/dL, so 120 mg/dL scores 0.

Hint
  1. Score each component separately against its own thresholds before adding them.
  2. The D-dimer component is scaled against the assay's own upper limit of normal.

Review Disseminated intravascular coagulation

Problem 2 of 3

A PF4-heparin immunoassay is positive on a patient with a low 4Ts score. What does this result mean?

The immunoassay detects binding antibody, and only a functional assay shows platelet activation. At a low pretest probability a positive screen is most often a false positive.

Read a positive PF4-heparin immunoassay as confirmed HIT

A PF4-heparin immunoassay detects binding antibody, including antibody that does not activate platelets. A functional assay such as the serotonin-release assay shows activation at low heparin that saturating heparin suppresses, which identifies a platelet-activating antibody. Testing starts only when the clinical 4Ts score is intermediate or high.

The immunoassay detects binding antibody, and many patients with a low 4Ts score carry antibody that does not activate platelets. The positive screen is read with the low pretest probability, and a functional assay confirms HIT when it is still suspected.

The immunoassay shows binding antibody only. Confirmation of HIT comes from a functional assay.

Hint
  1. Ask what the immunoassay detects, and what a low pretest probability changes about how a positive result is used.
  2. Pretest probability changes what a positive screen means.

Review Thrombophilia and heparin-induced thrombocytopenia

Problem 3 of 3

A patient on rivaroxaban has an anti-Xa result reported from a heparin-calibrated assay. The care team wants to use it to judge whether the drug level is therapeutic. What do you tell them?

A heparin-calibrated anti-Xa assay is falsely raised by rivaroxaban and does not give a quantitative rivaroxaban level.

Reported a DOAC level from a heparin-calibrated anti-Xa

Anti-Xa results are quantitative only against the drug's own calibrator. Apixaban or rivaroxaban falsely raises a heparin-calibrated anti-Xa result, and PT or APTT cannot quantify either drug. A drug-calibrated anti-Xa measures direct Xa inhibitors, and a dilute thrombin time or ecarin-based assay measures dabigatran.

Anti-Xa results are quantitative only against the drug's own calibrator. A rivaroxaban-calibrated anti-Xa assay is the test that answers this question.

The PT gives a variable, reagent-dependent response to direct oral anticoagulants and cannot quantify concentration.

Review Anticoagulant measurement

Use it

  • A woman with metastatic adenocarcinoma and new sepsis (MRN 0083517) has a coagulation and platelet panel ordered from the intensive care unit.
  • She has no history of a bleeding or platelet disorder.
  • She was started on prophylactic heparin 3 days ago.
TestResultPreviousReference intervalFlag
Platelet count38 × 10³/µL165 × 10³/µL3 days ago150–450 × 10³/µLLow
PT17.2 s12.9 s3 days ago11.5–14.5 sHigh
Fibrinogen92 mg/dL310 mg/dL3 days ago200–400 mg/dLLow
D-dimer9 × ULN<1 × ULN × ULNHigh

Specimen: H 4, L 6, I 2. Citrate plasma and EDTA whole blood, both correctly filled.

Decision 1 of 3

How do you read this pattern?

Platelets, PT, and fibrinogen have all moved in the direction DIC produces, over 3 days, with sepsis as a compatible trigger. This panel carries more than one raised result.

Read a raised D-dimer alone as DIC

D-dimer rises with inflammation, surgery, trauma, pregnancy, cancer, and age. DIC needs a compatible trigger with falling platelets, a lengthening PT, raised D-dimer, and falling fibrinogen, scored and trended with the ISTH overt-DIC score. A single raised D-dimer overcalls DIC.

Sepsis is a recognized DIC trigger. Platelets fell from 165 to 38 × 10³/µL, the PT lengthened, D-dimer rose to 9 times the upper limit of normal, and fibrinogen fell from 310 to 92 mg/dL, the combination the score is built to capture.

The timing is early for HIT, which commonly begins 5 to 10 days after a new exposure, and the prolonged PT and falling fibrinogen do not fit a HIT-alone picture.

Review Disseminated intravascular coagulation

Decision 2 of 3

The team asks whether the low platelet count could also be heparin-induced thrombocytopenia (HIT). What do you tell them?

The timing here, 3 days after a new heparin exposure, together with the DIC-compatible pattern already present, is scored with the other 4Ts elements before a PF4-heparin immunoassay is ordered.

Testing without regard to pretest probability, when the timing and the rest of the picture already point elsewhere, risks a false-positive result being acted on as HIT.

Three days can still occur with recent prior heparin exposure, so timing alone does not rule HIT out. The 4Ts score weighs the day count together with the rest of the picture.

Review Thrombophilia and heparin-induced thrombocytopenia

Decision 3 of 3

A repeat panel 6 hours later shows the platelet count and fibrinogen both falling further, with the D-dimer still high. What does this trend add?

Serial direction carries more information than a single value in consumptive disease. A worsening trend strengthens the pattern beyond what one panel shows.

Read a raised D-dimer alone as DIC

D-dimer rises with inflammation, surgery, trauma, pregnancy, cancer, and age. DIC needs a compatible trigger with falling platelets, a lengthening PT, raised D-dimer, and falling fibrinogen, scored and trended with the ISTH overt-DIC score. A single raised D-dimer overcalls DIC.

A falling platelet count and fibrinogen over time, with a persistently high D-dimer, show active, ongoing consumption. The score is reassessed with the trend in view.

A high, unchanged D-dimer alongside worsening platelets and fibrinogen does not show resolution. Falling platelets and fibrinogen are the more informative direction here.

Review Disseminated intravascular coagulation

The clue that settles this case is the trend across the panel and its repeat: platelets and fibrinogen both falling, with a high D-dimer and a lengthening PT, against a compatible trigger of sepsis. That combination is the pattern the DIC score is built to capture.

Keep

Sources checked