Coach’s Corner

About Coach’s Corner

In the best of all worlds, clinical practice guidelines provide recommendations about diagnosis and treatment that are based on solid evidence from phase 3 clinical trials. In many cases, such evidence does not exist and recommendations are provided based on expert opinion. Even then, many questions pertinent to clinical care may be left out of guidelines. In Coach’s Corner, we aim to address some of these gaps by surveying the opinion of clinical experts from the TBP board of advisors in areas where there exists a gray zone. This exercise is not meant to provide definitive guidance for patient care, but rather is designed to highlight the importance of clinical experience and critical thinking in the decision making process.

The opinions presented in this case were obtained in June 2022, and may be subject to change as new evidence emerges.

Question 1

Background:

Guideline statements vary on how to interpret moderately or strongly positive enzyme immunoassay results in w/o for HIT:

• 2012 ACCP guideline states that if immunoassay result > 1 OD and intermediate or high 4T score, accuracy of combined testing may be similar to functional assay (the latter not being necessary to order), whereas functional assay is recommended if OD 0.4-1.0.
• 2018 ASH guideline states that a functional assay may not be necessary for patients with a high-probability 4Ts score and very strongly positive immunoassay (e.g., an ELISA value of 2.0 OD units). 

Question: Is there a threshold OD on the immunoassay above which you do not order a functional assay (i.e., you would assume it to be positive)?

Anish V. Sharda, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Anish’s answer

OD > 1.0 with high-probability score; SRAs are highly specific but less so sensitive.

Brian J. Carney, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Brian’s answer

I don’t have a threshold OD above which I would never order a functional assay. I always consider both OD and pretest probability from the 4T score when deciding on whether or not to send SRA. If the 4T score is high and OD > 1, I usually don’t recommend a functional assay.

William C. Aird, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Bill’s answer

If the immunoassay is positive in someone with intermediate-high probability 4T score, I order an SRA no matter how high the OD.

Peter L. Gross, MD

Thrombosis Service, Hamilton Health Sciences, McMaster University

Click for Peter’s answer

We have an in-house SRA that is done twice a week. We rarely get the immunoassay before the SRA, but a high immunoassay result  (> 1 OD) with a high 4T score will make the diagnosis while waiting. The only alteration would be escalation of the anticoagulant dose from prophylaxis to therapeutic if the patient did not have a clot.

Question 2

Background: There are various immunoassays available for detecting heparin-dependent antibodies. They include enzyme immunoassays (EIA) and latex immunoturbidimetric assays (LIA). They are both highly sensitive for detecting pathological heparin-induced thrombocytopenia (HIT) antibodies. There is a better-established correlation between strength of enzyme immunoassay (OD) and HIT than there is between LIA results and HIT, but testing for EIA occurs in batches and takes longer for results to come back. 

We asked our experts: 

Question: Given these trade-offs, which type of assay do you prefer to use?

Anish V. Sharda, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Anish’s answer

I prefer enzyme immunoassays as these are more sensitive and ODs are more reliable; but these take longer to come back. Latex immunoassays may also miss rare protamine/heparin-induced thrombocytopenia.

Brian J. Carney, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Brian’s answer

I prefer the EIA given better correlation with HIT. While batched, turnaround time is usually within 24 hours at my institution.

William C. Aird, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Bill’s answer

Our institution recently switched from enzyme immunoassay to latex immunoturbidimetric assay (LIA). I like the rapid turnaround time with the LIA, but I am less comfortable using the semi-quantitative results to guide further work-up/therapy.

Peter L. Gross, MD

Thrombosis Service, Hamilton Health Sciences, McMaster University

Click for Peter’s answer

We use EIA, I have no experience with latex methods. The batch issue is cost only because it comes in strips.

Question 3

We asked our experts:

Question: You have a patient with a high 4T score, positive HIT antibodies and negative SRA. Do you stop the non-heparin anticoagulant and resume heparin?

Anish V. Sharda, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Anish’s answer

No. SRAs are not as sensitive as heparin/PF4-dependent antibody assays. High probability score + high OD = HIT.

Brian J. Carney, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Brian’s answer

I would continue the non-heparin anticoagulant and repeat the HIT antibody. If it is again positive, I would treat as HIT.

William C. Aird, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Bill’s answer

I would continue the non-heparin anticoagulant and repeat the assay.

Peter L. Gross, MD

Thrombosis Service, Hamilton Health Sciences, McMaster University

Click for Peter’s answer

Yes.  I would follow and retest in a couple of day though.

Question 4

Background: Regarding the use of DOAC in HIT, the 2018 ASH guideline states: “When a nonheparin anticoagulant is being selected, the ASH guideline panel suggests argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant (DOAC).” They then go on to write: “In patients with HIT complicated by life- or limb-threatening thromboembolism (e.g., massive pulmonary embolism or venous limb gangrene), a parenteral non-heparin anticoagulant may be preferred because few such patients have been treated with a DOAC.”

Question: Under what circumstances are you comfortable treating HIT with DOAC – do you draw the line at HITT or HITT with high clot burden, or are all patients fair game?

Anish V. Sharda, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Anish’s answer

I feel comfortable treating all patients with DOACs. Sick patients usually end up getting parenteral direct thrombin antagonists initially.

Brian J. Carney, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Brian’s answer

​I am comfortable using DOACs for HIT without thrombosis. I will consider a DOAC for HIT with low-risk VTE. I use an IV direct thrombin inhibitor with bridge to warfarin for patients with HIT with higher risk VTE and/or arterial thrombosis.

William C. Aird, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Bill’s answer

I am comfortable using DOACs in patients with HIT provided there is not a large clot burden. However, my preference is to use fondaparinux, assuming normal renal function.

Peter L. Gross, MD

Thrombosis Service, Hamilton Health Sciences, McMaster University

Click for Peter’s answer

Our initial drug of choice for HIT is fondaparinux. If in the context of thrombosis once they are improving on fondaparinux, weeks maybe, we switch to DOAC.  For patients where HIT is suspected, depending on the clinical situation, a prophylactic DOAC dose might be used as prophylaxis while waiting for the test instead of fondaparinux,  especially if the patient is an outpatient or will be discharged soon – fondaparinux is very expensive and not covered in Ontario Canada. Also in HIT without thrombosis full dose DOAC is the usual treatment.

Question 5

Background: Regarding duration of therapy, the 2018 ASH guideline states that in a patient with HITT, anticoagulation should be continued for 3 months. However, in a patient with HIT and no thrombosis, they say to continue anticoagulation, at a minimum, until platelet count recovery (usually a platelet count of >150 x 109 /L) – in other words, there is no recommendation for specified length of treatment (e.g., 3 weeks or 6 weeks), leaving open the possibility of no anticoagulation once platelet count recovers. 

Question: What is your approach in this regard, and are you generally comfortable transitioning to DOAC rather than VKA? 

Anish V. Sharda, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Anish’s answer

In HIT without thrombosis, I am comfortable using DOAC for a total of 6 weeks. Post-op patients, which are majority of the bonafide HIT cases, have an increased risk of post-op events (2-4 weeks; depending on the nature of the surgery) and HIT increases it by at least a few-folds. So, 4-6 weeks is justifiable. Personally, I hate when patients clot, but am okay with managing bleeding!

Brian J. Carney, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Brian’s answer

I recommend anticoagulation for 6 weeks in patients with HIT without thrombosis. I usually use a DOAC if no compelling reason not to.

William C. Aird, MD

Hematology, Beth Israel Deaconess Medical Center; Harvard Medical School

Click for Bill’s answer

I generally anticoagulate patients with HIT without thrombosis for 6 weeks, and those with thrombosis (HITT) for 3 months. I prefer DOAC in both situations.

Peter L. Gross, MD

Thrombosis Service, Hamilton Health Sciences, McMaster University

Click for Peter’s answer

HIT without thrombosis is treated with full dose DOAC for 3 months.