Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. List the diagnostic criteria for TTS
2. Describe the treatment for TTS

Estimated time to complete activity: 0.25 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

Faculty: Susan J. Gross, MD, receives consulting fees from Cradle Genomics, and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from through , participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.25 contact hours.

Designated for 0.1 contact hours of pharmacotherapy credit for Advance Practice Registered Nurses.

Read Disclaimer & Fine Print

SUMMARY:

Although very rare, thrombosis with thrombocytopenia syndrome (TTS) has been associated with AD26.COV2.S (J&J) vaccine in the US and similar events have been documented outside the US with use of the CHaDOx1 nCov-19 (AstraZeneca) vaccine. This syndrome has been referred to by alternate names in the literature, including vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or ‘vaccine-induced immune thrombotic thrombocytopenia (VITT)’. TTS is being used by the FDA and CDC. The American Society of Hematology has provided guidance on diagnosis and when to refer.

TTS Diagnostic Criteria

• All 4 criteria must be met
  • J&J or AstraZeneca vaccine within 4 to 30 days
  • Venous or arterial thrombosis (often cerebral or abdominal)
  • Thrombocytopenia (current TTS definition <150,000/μL)
  • Positive PF4 ‘HIT’ (heparin-induced thrombocytopenia) ELISA

Note: In early stage of TTS, thrombosis may be present prior to platelet count decrease

Clinical Findings

• Severe headache
• Visual changes
• Abdominal pain
• Nausea and vomiting
• Back pain
• Shortness of breath
• Leg pain or swelling
• Petechiae, easy bruising, or bleeding

Work-Up

Labs

1. CBC with platelet count and peripheral smear
   • Mean platelet count in published reports: 20,000/μL | There is a range from profound to mild
2. D-dimers: Most patients have significantly elevated levels
3. Fibrinogen: Some patients have low levels
4. PF4-heparin ELISA: almost all cases reported have positive assays | Most will have optical density >2.0 to 3.0

Note: Do not use non-ELISA rapid immunoassays for HIT | Non-ELISA tests are not sufficiently sensitive nor specific for TTS

Imaging for Thrombosis

• Imaging based on symptoms
• Focus on cerebral sinus venous thrombosis (CSVT) with use of CT or MRI venogram
• Patients may also have splanchnic thrombosis, pulmonary emboli, and/or DVT

Treatment

• IVIG 1 g/kg daily for two days
• Non-heparin anticoagulation
  • Parenteral direct thrombin inhibitors (argatroban or bivalrudin if aPTT is normal) or
  • Direct oral anticoagulants without lead-in heparin phase or
  • Fondaparinux or
  • Danaparoid

When to Treat

While waiting for PF4 ELISA

• Begin IV immune immunoglobin and nonheparin anticoagulation if there is clinical evidence of serious thrombosis AND ≥1 of the following
  • Positive imaging
  • Low platelets
• If PF4 ELISA returns negative and there is no thrombocytopenia, TTS is ruled out
  • Treat for venous thromboembolism using standard protocols

KEY POINTS:

• TTS is suspected
  • Obtain immediate CBC with platelet count and imaging for thrombosis based on symptoms
  • If thrombosis and/or thrombocytopenia is present, referral to hematologist with expertise in hemostasis is recommended
• Do not use non-ELISA rapid immunoassays for HIT
• Avoid heparin until TTS ruled out or other reasonable diagnosis has been established
• In addition

If thrombocytopenia but no thrombosis and negative PF4 ELISA, likely ITP

Microangiopathy with red cell fragmentation and hemolysis have not been features of reported cases, thus distinguishing this syndrome from TTP/HUS is straightforward

Avoid platelet transfusions unless other treatments have been initiated AND life-threatening bleeding or imminent surgery

Consider referral to tertiary care center if TTS is confirmed

Learn More – Primary Sources:

American Society of Hematology: Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia)

Related ObG Topics:

J&J Vaccine Report: Rare Thrombosis and Thrombocytopenia Responsive to IV Immune Globulin

SMFM Guidance on COVID-19 Vaccine in Pregnancy

Potential Pathology Behind AstraZeneca COVID-19 Vaccination and Blood Clots