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The monitoring of heparin induced thrombocytopenia following surgery: an audit and international survey.

Introduction

Low-molecular-weight heparin (LMWH) is widely used in the prevention of thromboembolism in orthopaedic patients, particularly those undergoing lower limb joint arthroplasty (Leyvraz et al 1991, Mohr et al 1993, Wolf 1994). Several types of LMWH are commonly used including enoxaparin (Clexane[R], Rhone-Poulenc Rorer), dalteparin (Fragmin[R], Pharmacia) and tinzaparin (Innohep[R], LEO), with bleeding and thrombocytopenia having been known complications (BNF 2008). Bleeding may occur at various locations: operative site, epidural, intrahepatic, and retroperitoneal sites, gastrointestinal tract (Antonelli et al 2000, Houde & Steinberg 1999, Shaieb et al 1999, Stern et al 2000). Intracerebral haemorrhage following the use of LMWH has occurred following neurosurgical and orthopaedic procedures, with serious consequences (Dickinson et al 1998, Lilikakis et al 2006).

Heparin-induced thrombocytopenia (HIT) is associated with thrombosis, independent of heparin type, dose or route of administration (Boshkov et al 1993, Chong 1995, King et al 1984). It results from an antibody-mediated response to heparin triggering a reduction in the platelet count (Burgess et al 1995, Gerhard-Herman 2001, Warkentin 1999). The British Society for Haematology (BSH) has produced evidence based guidelines for the identification and management of heparin-induced thrombocytopenia (Baglin et al 2006). In summary the guidelines advocate:

1. All patients require a platelet count on day of starting treatment.

2. Repeat platelet counts should be repeated every 2-4 days from days 4-14.

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This study audits the implementation and awareness of these guidelines within an orthopaedic unit and compares current practice both in the UK and internationally.

Methods

An audit loop consisting of two sequential surveys detailing the monitoring of at-risk patients was performed before and after the introduction of an evidence based protocol for the monitoring of heparin induced thrombocytopenia--see figure 1. Enoxaparin (Clexane[R], Rhone-Poulenc Rorer) was the only LMWH prescribed for patients in this study. Hospital and departmental approval was obtained prior to commencing this audit. Patients who were medically unwell or commenced on warfarin were excluded since their inclusion would not accurately reflect routine HIT monitoring.
Figure 2: Protocol implemented following initial survey

Guidelines on management of heparin-induced thrombocytopenia

1. All patients who receive heparin (of any sort) should have a
   platelet count on day of starting treatment

2. All surgical patients receiving LMWH, platelet counts should be
   performed every 2-4 days from days 4--14

3. If platelet count falls by over 50% or below normal lab limits
   consider HIT, stop heparin and inform haematologist


[FIGURE 3 OMITTED]

[FIGURE 4 OMITTED]

The initial 48 patients who received LMWH for longer than 4 days included 35 operative fixations of proximal femoral fractures, one open reduction and internal fixation of a distal femoral fracture, and 12 lower limb joint arthroplasties. The mean average age was 78 years (range 64-93 years), with 29 female and 16 male. The results of the initial survey were compared with the evidence based British Society for Haematology guidelines (Baglin et al 2006) and discussed at a departmental meeting. A protocol recommending a platelet count every 2-4 days in at-risk patients was implemented (see figure 2). A subsequent survey of 53 patients was conducted, with a mean age of 76 years (range 52--89 years), with 20 male and 28 female.

A telephone survey questioning awareness of heparin induced thrombocytopenia and the recent BSH guidelines was conducted. Statistical analysis of the results was carried out using a chi-square test with SPSS v12.0 for Windows.

Results

The initial patient survey demonstrated that only 2 out of 48 at-risk patients (4%) had a full blood count (FBC) performed more than four days after commencing LMWH--see figure 3.

The second survey demonstrated a significant improvement (p<0.05), with 23 out of 40 (57.5%) at-risk patients having a FBC performed more than four days after commencing LMWH--see figure 4.

The secondary survey demonstrated a significant improvement (p<0.05) in the monitoring of HIT compared with the primary survey (57.5% compared to 4%)see figure 5.

[FIGURE 5 OMITTED]

[FIGURE 6 OMITTED]

From the secondary survey, 23 out of 40 patients had platelet count monitoring as outlined by the BSH guidelines. The quantitative change in the platelet count seen in these patients is shown in Figure 6. The postoperative platelet count dropped below 75% of the preoperative level in 13 out of the 23. Two patients demonstrated a reduction of over 50% in the platelet count that responded with the subsequent cessation of LMWH.

A telephone survey of registrars/interns from 46 orthopaedic units (34 district general/community hospitals, 12 teaching hospitals) in 5 countries (England, France, Scotland, Canada and USA) was conducted. There was a low awareness of both the condition of heparin-induced thrombocytopenia and the BSH guidelines and no units routinely monitored for HIT (see Table 1).

Discussion

Low molecular weight heparins have been used to reduce thromboembolic risk in both primary care and the hospital setting for at least twenty years (Clagett et al 1995, Imberti et al 2006, Mohr et al 1993, Wolf 1994). Whilst providing an effective pharmacological thromboprophylaxsis, their use in orthopaedic surgery is not without risk (Bickler et al 2006, Lilikakis et al 2006, Stern et al 2000).

This clinical audit demonstrates a significant improvement in platelet count monitoring for patients at risk of heparin-induced thrombocytopenia by the implementation of a simple protocol and an additional full blood count (approximately 1 [pounds sterling] per test). However, with nearly 50% of at-risk patients still not being monitored, improvements are still needed. The international survey highlights an ongoing lack of awareness regarding heparin-induced thrombocytopenia and the necessary monitoring of platelet counts.

All prescribers of prescription only medications should be aware not only of the common side effects but also of the rare adverse reactions that may have serious consequences. Following the publication of case reports showing intracranial haemorrhages as a consequence of heparin-induced thrombocytopenia (Lilikakis et al 2006) and evidence based guidelines (Baglin et al 2006), failure to routinely monitor for thrombocytopenia in patients receiving LMWHs may have medico-legal implications.

The conclusions of this study are:

1. Heparin-induced thrombocytopenia is a rare but potentially fatal complication of low molecular weight heparin.

2. Few orthopaedic units are currently aware of the risk of heparin-induced thrombocytopenia when prescribing LMWH.

3. The introduction of a simple monitoring protocol can facilitate its early identification and treatment.

KEYWORDS Heparin induced thrombocytopenia (HIT) / Monitoring / Survey

Provenance and Peer review: Unsolicited contribution; Peer reviewed; Accepted for publication September 2009.

References

Antonelli D, Fares L, Anene C 2000 Enoxaparin associated with huge abdominal wall hematomas: a report of two cases The AmericanSurgeon 66 (8) 797-800

Baglin T, Barrowcliffe TW, Cohen A, Greaves M 2006 Guidelines on the use and monitoring of heparin British Journal of Haematology 133 (1) 19-34

Bickler P, Brandes J, Lee M, Bozic K, Chesbro B, Claassen J 2006 Bleeding complications from femoral and sciatic nerve catheters in patients receiving low molecular weight heparin Anesthesia & Analgesia 103 (4) 1036-1037

Boshkov LK, Warkentin TE, Hayward CP, Andrew M, Kelton JG 1993 Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies British Journal of Haematology 84 (2) 322-328

British National Formulary 2008 London, BMJ Publishing

Burgess JK, Lindeman R, Chesterman CN, Chong BH 1995 Single amino acid mutation of Fc gamma receptor is associated with the development of heparin-induced thrombocytopenia British Journal of Haematology 91 (3) 761-766

Chong BH 1995 Heparin-induced thrombocytopenia British Journal of Haematology 89 (3) 431-439

Clagett GP, Anderson FA Jr, Heit J, Levine MN, Wheeler HB 1995 Prevention of venous thromboembolism Chest 108 (4 Suppl) 312S-334S

Dickinson LD, Miller LD, Patel CP, Gupta SK 1998 Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors Neurosurgery 43 (5) 1074-1081

Gerhard-Herman M 2001 Heparin-induced thrombocytopenia Current Treatment Options in Cardiovascular Medicine 3 (3) 215-224

Houde JP, Steinberg G 1999 Intrahepatic hemorrhage after use of low-molecular-weight heparin for total hip arthroplasty Journal of Arthroplasty 14 (3) 372-374

Imberti D, Ageno W, Dentali F, Giorgi PM, Croci E, Garcia D 2006 Management of primary care patients with suspected deep vein thrombosis: use of a therapeutic dose of low-molecular-weight heparin to avoid urgent ultrasonographic evaluation Journal of Thrombosis and Haemostasis 4 (5) 1037-1041

King DJ, Kelton JG 1984 Heparin-associated thrombocytopenia Annals of Internal Medicine 100 (4) 535-540

Leyvraz PF, Bachmann F, Hoek J et al 1991 Prevention of deep vein thrombosis after hip replacement: randomised comparison between unfractionated heparin and low molecular weight heparin British Medical Journal 303 (6802) 543-548

Lilikakis AK, Papapolychroniou T, Macheras G, Michelinakis E 2006 Thrombocytopenia and intracerebral complications associated with low-molecular-weight heparin treatment in patients undergoing total hip replacement. A report of two cases Journal of Bone and Joint Surgery (Am) 88 (3) 634-638

Mohr DN, Silverstein MD, Murtaugh PA, Harrison JM 1993 Prophylactic agents for venous thrombosis in elective hip surgery. Meta-analysis of studies using venographic assessment Archives of Internal Medicine 153 (19) 2221-2228

Shaieb MD, Watson BN, Atkinson RE 1999 Bleeding complications with enoxaparin for deep venous thrombosis prophylaxis Journal of Arthroplasty 14 (4) 432-438

Stern SH, Wixson RL, O'Connor D 2000 Evaluation of the safety and efficacy of enoxaparin and warfarin for prevention of deep vein thrombosis after total knee arthroplasty Journal of Arthroplasty 15 (2) 153-158

Warkentin TE 1999 Heparin-induced thrombocytopenia: a clinicopathologic syndrome Thrombosis and Haemostasis 82 (2) 439-447

Wolf H 1994 Low-molecular-weight heparin Medical Clinics of North America 78 (3) 733-743

Mr Benedict A Rogers MA, MSc, MRCGP, FRCS(Orth)

Specialist Registrar, Trauma and Orthopaedics, East Surrey Hospital, Redhill, Surrey

Mr Andrew Stuart Cowie MBBS BSc(Hons) MRCS(Eng)

Specialist Registrar, General Surgical Rotation, Wessex Deanery, Poole Hospital NHS Foundation Trust

No competing interests declared

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Correspondence address: Mr B A Rogers, Trauma & Orthopaedics, St George's Hospital, Tooting, London, SW17 0QT. Email: benedictrogers@hotmail.com
Table 1: Survey assessing the awareness of the BSH guidelines for
heparin-induced thrombocytopenia

                       Aware     Aware of     Monitor platelet
                       of HIT    BSH HIT     count for patients
                                guidelines        on LMWH

District general/       5/34       1/34             0/34
  community hospital
Teaching hospital       6/12       1/12             0/12
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Article Details
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Title Annotation:RESEARCH & AUDIT
Author:Rogers, Benedict A.; Cowie, Andrew S.
Publication:Journal of Perioperative Practice
Article Type:Report
Geographic Code:1USA
Date:Feb 1, 2010
Words:1703
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