Purpose 100 (100)

Heparin-induced thrombocytopenia (HIT), a hypercoagulable state, is an adverse drug reaction

involving antibodies that form to platelet factor 4 bound to a polyanion, generally heparin. This
complex activates the platelet FcyRIIA receptor to generate a hypercoagulable condition.
Autoimmune HIT (aHIT), not commonly recognized, is a subset of HIT that occurs in patients
that have heparin-independent antibodies. The condition can cause thrombotic complications and
death. aHIT does not always respond to non-heparin anticoagulants, thus intravenous
immunoglobulin (IVIG) is being used to treat patients with aHIT. This review evaluated the
efficacy, safety, and place in therapy of IVIG in patients with aHIT.
Methods 225 (216)
A literature search was conducted using Pubmed and CINAHL databases to find literature using
IVIG to treat aHIT published between January 1, 2017 to June 1, 2020. Search terms used
included: HIT, autoimmune HIT, IVIG, severe HIT, fondaparinux associated aHIT, flush aHIT,
spontaneous aHIT, delayed aHIT, and persisting aHIT. The American Society of Hematology
(ASH) guidelines were also utilized to provide background information on HIT. The literature
was reviewed to assess the following: patient age, sex, initial anticoagulant used, HIT
anticoagulant used, aHIT syndrome diagnosis, nadir platelet count, platelet count when IVIG
was initiated, reported peak platelet count post IVIG treatment, dose of IVIG, and response to
IVIG. The aHIT syndromes are defined as follows: delayed-onset aHIT that begins or worsens
after discontinuation of heparin, persisting aHIT that persists for greater than 1 week despite
discontinuation of heparin, spontaneous-onset aHIT without proximate heparin exposure, flush
induced aHIT that is initiated by exposure to heparin flushes, and fondaparinux-associated aHIT
that is thought to be triggered by fondaparinux therapy. Response to IVIG was classified as
either excellent (a platelet count rise by at least 100 x 109/L), good (a rise in platelet count by 50-
99 x 109/L), or poor (a rise in platelet count of less than 50 x 109/L) after administration of 1
week of IVIG therapy.
Results 200 (198)
Literature identified for this review included 19 retrospective case reports (23 patients, 13 males
and 10 females). The ages ranged from 30-84 years old (mean= 60.65 years old). Unfractionated
heparin was used in 20 patients (87%) and low molecular weight heparin was used in 9 patients
(39%). Anticoagulants used for HIT treatment were: argatroban (69.5%), fondaparinux (30%),
bivalirudin (17.4%), dabigatran (4.3%), and danaparoid (4.3%). There were 8 cases of persisting
HIT, 1 case of delayed-onset, 2 cases of spontaneous HIT, 8 cases of delayed/persisting HIT, 1
case of delayed/spontaneous, 1 case of fondaparinux-associated, 1 case of flush heparin HIT, and
1 did not meet criteria of aHIT. The nadir platelet count ranged from 1x109/L to 93x109/L
(mean= 22.3x109/L). The IVIG dose of 1 gm/kg x 2 consecutive days was the most common
dose with 10 cases utilizing this dose. The duration of therapy ranged from 1 day to 7 days
(mean= 2 days). The peak platelet count post IVIG dose ranged from 50 x 109/L to 355 x 109/L
(mean= 158 x 109/L). An excellent response was seen in 13 cases, a good response was seen in 6
cases, and a poor response was seen in 4 cases.
Conclusion 100 (98)
IVIG used for aHIT provided consistent increases in platelet count and prevented complications.
Patients received different IVIG doses, but the most common dose was 1 gm/kg for 2
consecutive days. Some patients who had received IVIG doses less than 1 gm/kg x 2 consecutive
days required repeat administrations. The increase in platelet count was seen within 2 days in
most cases. With the lack of recognition of aHIT and its treatments it is prudent for the heparin
induced thrombocytopenia guidelines to continue to study the role of IVIG and to understand its
effectiveness, safety, and place in therapy.