Acute Massive Postoperative Atria1 Thrombosis in a Patient Undergoing Low Molecular Weight Heparin Anticoagulation

Ruggero De Paulis, MD, Jean Pierre Fleury, MD, Lynn Veyssie, MD, Philippe Menasche, MD, PhD,

Gerard Block, MD, Armand Piwnica. MD

D URING THE first 3 months following mitral valve

replacement (MVR) with a bioprosthetic valve, mod- erate anticoagulation is required. Sodium warfarin is usu- ally the drug of choice. Most of the time, heparin is used during the first postoperative week before an adequate anticoagulation lcvcl is obtained with sodium warfarin. Recently, a low molecular weight heparin (LMWH) be- came clinically available; it has good antithrombotic proper- ties along with a reduced risk of hemorrhagic complications and is more conveniently and practically administered than unfractionated heparin. Reports have detailed its success- ful use in the prevention of thrombosis following general or orthopedic surgery.‘,’ Others have demonstrated its safe and effective use in hemodialysis and hemofiltration pa- tients.”

Encouraged by these results, the authors extended its use for prophylaxis against atria1 thrombosis in the immediate postoperative period following valve replacement. This is the first report of the use of LMWH in this clinical setting.

Unfortunately, an acute massive left atrial thrombosis occurred in the early postoperative period after MVR with a bioprosthesis in the patient.

CASE REPORT

A 76-year-old woman with exertion and rest dyspnea was admitted to the hospital. The clinical history showed three previous episodes of acute pulmonary edema; atria1 fibrillation had devel- oped a few months before admission. Physical examination and echocardiography showed mitral stenosis with a valve area of 1.1 cm? and a dilated left atrium. Pulmonary scintigraphy showed hypoperfusion in the distal right lung probably due to peripheral pulmonary emboli. Thrombophlebitis was ruled out by a Doppler study.

She was receiving unfractionated heparin (12,500 IU) that was administered subcutaneously twice a day and the activated partial thromboplastin time was twice control values. The patient under- went MVR with a size 30 Liotta porcine heterograft. For cardiopul- monary bypass (CPB), a membrane oxygenator and a peristaltic pump were used; the patient received a full dose (300 U/kg) of heparin that was neutralized with an equivalent dose of protamine at the end of cardiopulmonary bypass. At the time of surgery there was no evidence of atrial thrombi.

Eight hours after operation she was started on LMWH (Fraxipa- rine, Choay, Paris) at the dose of 7,500 U of anti-Xa daily (134 U/kg) administered subcutaneously. The clinical course was un- eventful until the second postoperative day when she developed increasing rest dyspnea. and the ECG revealed atria1 fibrillation.

From Chirutgie Curdiovasculaire. H6pital Larihoisiere, Puris, France, and the University of Tor Verguta. Rome, Itu!y.

Address reprint request to Dr. Ruggero De Paulis. Division of Cardiac Surgev, European Hospital, via Portuensc 694, 00149 Roma,

Italy. Copyright K? 1993 by W.B. Saunder.s Company 1053-0770/4310703-0016$03.00/0 Kqv words: low molecular weight heparin, atria1 thrombosis, antico-

agulation

I‘he next 3 days hcl- general conthtlon progressively dctcriot-alcd until \he developed acute pulmonary edema requiring tracheal intuhation and mechanical ventilation. The pulse was irregular ,~t 130 heats/minute. heart sound wcrr normal, and no mucocutnnc- ous signs of systemic cmboli were found. Platelet count was normal and the activated coagulation time (ACT) was I.5 times the contl-ol value. Two-dimensional echocardiography from different ~L‘OIISII- cal windows tailed to demonstrate the presence of an atrIal thromhus. However. transesophagcal echocardiography (TEE) showed a reduced Left atrial cavity with the atrial walls bclng covered with thick mural thromhi (Fig I ). Inside the residual atrial cavity. spontaneous and turbulent contra\t was seen along lrlth ‘1 normally functioning mitral valve (Fig 2). AI that time. the cardiac index dropped to 1.7 I_,min and the pulmonary capillary wcdg~ pressure was 20 mmFlp.

The patient underwent urgent \urgicail exploration: ‘t lett ‘III-lot- omy was performed with CPB and a 3 x 4 cm thrombus popped out. It had a smooth surface without signs of attachment to the atrial wall. Careful examination of the atrial cavity revealed tbr markings of the prohable prior attachment to the atrial waII in either the appendage or a small portion of the valve stent. The prosthetic valve was left in place. Following the second operation, the patient received IV heparin until a good level of anticoagul;l- tion was obtained with sodium warfarin. She recovered unevent-

fully and was discharged home.

DISCUSSION

In this report three observations arc noteworthy: (1) An

acute massive left atria1 thrombosis occurred in the early postoperative period after MVR; (2) TEE was an invalu- able diagnostic tool in this unusual cast; and (3) the use of LMWH in the prevention of left atria1 thrombosis.

A massive left atrial thrombosis is highly uncommon. It has been associated with a severely enlarged left atrium usually in combination with abnormality of the mitral valve or as a complication of MVR.J-5 Its pathophysiologic effects are mainly due to obstruction of fow through the mitral valve, and a clinical picture of pulmonary edema, heart failure. severe rhythm disorders, systemic emboli. and sudden death usually results. In this particular cast, the thrombus nearly tilled the left atrial cavity. and, therefore. did not move. This aspect might explain the difficult& that were encountered in echocardiographically identifying the anatomical contours of the thrombus. Furthermore, it should be underlined that the age of the thrombus might also have limited accurate detection of its anatomical shape.’ However, the high definition of TEE avoided the drawback of transthoracic echocardiography. The detection of a very large atria1 thrombus made by echocardiography in the presence of compromised hemodynamics indicated prompt surgical intervention.

The use of LMWHs is based on the fact that they have a different anticoagulation profile than unfractionated hepa- rin. They have the theoretical advantage of dissociating the antithrombotic and hemorrhagic properties with the result of less hemorrhage for equivalent antithrombotic effects.” Heparin inhibits blood coagulation by augmenting the

332 Journalof Cardiothoracic and Vascular Anesthesia, Vol 7, No 3 (June), 1993: pp 332-334

ATRIAL THROMBOSIS DURING LMW HEPARIN THERAPY 333

!sence of a thrombus

effect of AT III,’ and, therefore, increasing the inhibitory

btoavatlabthty ot LMWHs IS about tour times higher than

effect of thrombinR while inhibiting the activation of pro- thrombin by Xa.” Furthermore, its damaging effects on platelets are well known.lO LMWHs are derived from a process of heparin fractionation and fragmentation that leads to production of substances with a molecular weight around 5,000. Like unfractionated heparin, LMWHs inhibit clotting enzymes by binding to AT III, but they lack additional chain length to bind to thrombin6 LMWHs seem to inhibit platelet function and increase vascular permeabil- ity less than unfractionated heparin.” Furthermore, the . . . . . ^ _ _ ___.-_ . . ^ . . .

unfractionated heparin. More specifically, anti-factor Xa activity (an antithrombotic marker) is about two to four

shown tdenttcal, it not better, emcacy ot LMWHs compared

times longer than for unfractionated heparin, whereas anti- factor IIa plasmatic half-life, (a bleeding marker) is only slightly longer than for unfractionated heparin.‘* There- fore, LMWHs could be administered as a single daily dose via the subcutaneous route with a definite safety advantage. Due to a greater inhibition of factor Xa than of thrombin activity, less interaction with platelets, longer half-life with a consequent reduced number of injections, LMWHs have suggested new therapeutic applications. Clinical trials have

. . ..^ . ^_ _ ___._-

Fig 2. TEE showing spontaneous and sinusoidal contrast due to the turbulent flow inside the left atrial cavity. Abbreviations: LA, left atrium; LV, left ventri- cle.

334 DE PAULIS t. Q

to unfractionated heparin in general surgical and orthope- dic patients, ‘Z but the role of LMWH in the prevention of intracardiac thrombosis has not been addressed.

Clinical experience has demonstrated that it is difficult to judge the appropriate doses of LMWH because ofinterindi- vidual variation,” and the difficulty in assessing the anti- thrombotic action by using routine laboratory assays. Al- though the ACT and PTT were slightly prolonged in this patient, their USC has not been demonstrated to be effica- cious for the monitoring of LMWH. especially after subcu- taneous injections. I3 A better wav to monitor the anticoagu- lation level is to determine the anti-factor Xa activity. The anti-Xa levels were not measured. However, some authors

have stressed that dcspitc clinical prophylactic ctficaz! (11 LMWHs for 24 hour\ after single suhcutancous adrninislr:i-

tion, the level of anti-X;! and anti-lla cvhihit no c\-\I\() response after h hours. and does not seem to correlate \~ith clinical efficacy or hlceding side cRects; ;I greater effect on

these tests is noted only after therapeutic doses I’ Thcrc fore, it is likely that the dosage used. although it is the one recommended by the manufacturer. was not adcquatc t’o~ this particular patient. A more careful evaluation is needed bcforc starting cardiac paticntn with an increased risk 01 thrombosis on LMWH. Beforc more experience can hc gained. accurate monitoring of the level of anticoagulation is desirable.

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