- Email: [email protected]
Disseminated thrombosis in primary antiphospholipid syndrome: MR findings
European Journal of Radiology 26 (1998) 244 – 247
Case report
Disseminated thrombosis in primary antiphospholipid syndrome: MR findings James M. Provenzale a,*, Charles E. Spritzer a, Rendon C. Nelson a, Thomas L. Ortel b a
Department of Radiology, Box 3808, Duke Uni6ersity Medical Center, Durham, NC 27 710 -3808, USA b Department of Medicine, Duke Uni6ersity Medical Center, Durham, NC 27 710, USA Received 23 October 1996; received in revised form 3 December 1996; accepted 9 December 1996
Abstract We report the MR imaging findings in a patient with primary antiphospholipid syndrome, adrenal infarction and widespread thrombosis involving abdominal, pelvic, and pulmonary vessels. This syndrome should be suspected in patients with thromboses and organ infarctions of otherwise undetermined etiology. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Antiphospholipid antibody; Thrombosis; Pulmonary embolism; Adrenal hemorrhage
1. Introduction
2. Case report
The antiphospholipid syndrome (APS) consists of recurrent thromboses, cardiac valvular abnormalities, recurrent fetal loss, livedo reticularis (a purplish mottling of the skin due to vascular insufficiency) and thrombocytopenia [1]. APS occurs in patients with antiphospholipid antibodies, which are immunoglobulins that cross-react with phospholipids within cell membranes and are associated with a hypercoagulable state. The major types of antiphospholipid antibodies are the lupus anticoagulant and anticardiolipin antibodies [1]. APS can be seen in both systemic lupus erythematosus (SLE) patients (secondary APS) and patients who lack SLE features (primary APS) [1]. An APS-related thrombotic event typically involves only one vessel. Rarely, thrombosis can simultaneously involve multiple vessels, sometimes accompanied by organ infarction [2]. We report such a patient in whom simultaneous involvement of multiple vessels and organs was shown by MR imaging.
A 27-year-old man developed left leg deep venous thrombosis (DVT) that was successfully treated with intravenous heparin followed by oral warfarin for 1 year. Family history was notable for a paternal uncle and paternal grandfather who died at ages 45 and 38 years, respectively, with ill-defined disorders of hypercoagulability. At age 34 years, the patient developed right leg DVT which was again treated with anticoagulant therapy. He was also noted to be thrombocytopenic but a lupus anticoagulant was reportedly not identified. Subsequently, he developed chronic venous stasis changes and poorly healing leg ulcers. A prolonged activated partial thromboplastin time (\150 s; normal, B 23.6–37.1 s) that did not correct with mix, suggestive of the presence of a lupus anticoagulant, and a markedly elevated lgG anticardiolipin antibody titer (2110 gpl; normal, B 16 gpl) were found. At the age of 38 years, he developed left external iliac vein occlusion despite warfarin therapy with an international normalized ratio (INR) of 4.7 (the INR is a normalization factor for the protime that uses a correction factor for
* Corresponding author. Tel.: +1 919 6847409; fax: + 1 919 6847138.
0720-048X/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S 0 7 2 0 - 0 4 8 X ( 9 6 ) 0 1 1 5 4 - 0
J.M. Pro6enzale et al. / European Journal of Radiology 26 (1998) 244–247
different sensitivities of reagents to factor VII so that protimes from different laboratories can be compared. An INR of 2.0–3.0 usually proves adequate in normal individuals). He was treated with therapeutic subcutaneous heparin for 6 months and warfarin was then restarted with the therapeutic goal of keeping his factor II level below 30%. One month later he developed left flank pain, nausea and diaphoresis. Contrast-enhanced abdominal CT showed mild stranding of the left perinephric fat with a normal adrenal gland and kidney. Numerous venous collateral channels were seen comprised of enlarged inferior mesenteric, ascending lumbar and subcutaneous veins. Ventilation/perfusion lung scan showed perfusion defects in the left lower lobe without ventilation defects, consistent with pulmonary emboli and thought to be the source of the patient’s left flank pain. The patient developed right upper quadrant pain 2 days later. A new right adrenal mass was seen at abdominal sonography that correlated on MR imaging with an inhomogeneous mass having regions of hyperintense and hypointense signal intensity relative to liver on unenhanced T1-weighted and T2-weighted images, consistent with hemorrhage (Fig. 1A). Adrenal insufficiency was documented by low serum cortisol levels (1 mcg/dl) and an abnormal cortrosyn stimulation test. Gradient echo images of the pelvis showed bilateral common femoral vein thrombosis, left common iliac vein occlusion and a small right common iliac vein (Fig. 1B) with collateral flow through enlarged inferior mesenteric, ascending lumbar and subcutaneous veins (Fig. 1C). Gradient echo images of the pulmonary vasculature showed a filling defect in the left pulmonary artery, consistent with a pulmonary embolus (Fig. 1D), confirmed at catheter angiography (Fig. 1E). Because both common femoral veins were thrombosed, pulmonary angiography was performed via the right jugular vein, which subsequently thrombosed during the next 24 h. Intravenous heparin therapy was started in an attempt to treat pulmonary embolism and prevent further thromboses. During a 2 month follow-up period, no new thrombotic events have occurred.
245
3. Discussion There is increasing evidence that antiphospholipid antibodies are associated with a hypercoagulable state that can result in recurrent thromboses and infarction of brain and other organs [1,3,4]. Our patient had major features of primary APS, i.e. unexplained thromboses in the presence of antiphospholipid antibodies and without clinical or laboratory features of SLE. The finding of collateral venous circulation within the abdomen and pelvis was evidence of longstanding venous occlusive disease. These vascular occlusions occurred despite a degree of anti-coagulation that would be therapeutic for individuals without a hypercoagulable state. The development of pulmonary embolism and jugular vein thrombosis while on warfarin therapy was further evidence of a hypercoagulable state. DVT of the legs is the most common form of venous thrombosis in APS patients and is often accompanied by pulmonary embolism. However, thrombosis of the deep veins of the thorax, neck, abdomen (as in our patient) and dural sinuses have also been reported [5]. Arterial thromboses in APS patients usually occur in the peripheral arteries but can be seen in virtually any arterial bed, most notably in arteries supplying the brain, kidneys and viscera. Our patient experienced multiple, nearly simultaneous, thromboses and infarctions. The complications in our patient were more severe than routinely seen in APS. However, even more widespread simultaneous thromboses can rarely occur, causing infarction of brain, kidneys and other organs, often resulting in death (so-called catastrophic APS) [2]. Adrenal hemorrhage, frequently bilateral, is an uncommon, but potentially lethal complication of APS [3,6]. Adrenal hemorrhage or infarction should be suspected in an APS patient with abdominal pain and evidence of adrenal insufficiency. The cause of adrenal hemorrhage in APS patients is not known with certainty and may differ between individuals. Adrenal vein thrombosis has been postulated as the precipitating event of adrenal hemorrhage in some APS patients [3]. Therefore, adrenal hemorrhage may be another mani-
Fig. 1. A 39-year-old man with antiphospholipid antibodies, a history of multiple DVTs and external iliac vein occlusion and new left flank pain followed 2 days later by right upper quadrant pain. (a) Unenhanced T1-weighted spin-echo (550/20/2 (TR/TE/excitations)) MR image (top) and T2-weighted (2200/80/1) MR image (bottom) in the axial plane shows large inhomogeneous mass involving the right adrenal gland (arrows) with regions of hyperintense and hypointense signal intensity relative to liver consistent with hemorrhage. The left adrenal gland has a normal appearance. CT performed 10 days earlier (not shown) showed a normal right adrenal gland. (b) Gradient echo (33/13/1/60° (flip angle)) MR image of the pelvis in the axial plane shows normal signal intensity within common iliac arteries (solid arrows). No signal is present in the expected location of left common iliac vein, consistent with iliac vein occlusion. A small right common iliac vein is seen (arrowhead). On lower images, no flow was seen within the right external iliac vein. Flow is seen within an enlarged inferior mesenteric vein (curved arrow). Collateral veins (open arrows) are seen within subcutaneous fat. (c) Gradient echo (33/13/1/60°) image of the lower abdomen in the axial plane shows enlarged ascending lumbar veins (arrow) and inferior mesenteric vein (arrowheads). Normal signal intensity is seen in the inferior vena cava (curved arrow). (d) Gradient echo (33/13/1/60°) MR image of the chest in the axial plane shows a region of decreased signal intensity in the left pulmonary artery (arrow) consistent with pulmonary embolism. (e) Catheter angiogram of left pulmonary artery shows multiple intraluminal filling defects (arrowheads) due to pulmonary emboli.
246
J.M. Pro6enzale et al. / European Journal of Radiology 26 (1998) 244–247
Fig. 1.
J.M. Pro6enzale et al. / European Journal of Radiology 26 (1998) 244–247
festation of the hypercoagulable state in our patient. However, like some other previously reported APS patients with adrenal hemorrhage [6], the hemorrhage in our patient occurred while on anticoagulant therapy, raising the possibility that adrenal hemorrhage is a complication of warfarin therapy in some cases. The risk of recurrent thrombosis in APS is high and there is evidence to suggest that many APS patients require higher doses of anti-coagulation (INR\ 3.O) than individuals without a hypercoagulable state [4]. Such was the case in our patient in whom recurrent thrombosis occurred despite an INR of 4.7. Adrenal hemorrhage is not a contraindication to restarting anticoagulant therapy. Previous reports have documented APS patients with adrenal hemorrhage who have resumed anticoagulant therapy without complication [6]. The hazards of vessel catheterization during a period of pronounced hypercoaguablility in our patient are underscored by development of jugular vein thrombosis following pulmonary angiography. However, MR imaging demonstrated all of the important APS complications of our patient in a noninvasive manner. MR imaging has been shown to be accurate in diagnosing venous thrombosis, with the veins of the thorax, abdomen and extremities being readily assessed without the use of intravenous contrast agents [7]. More recently, MR imaging has shown promise as a noninvasive technique for detection of PE [8], as was also shown in our
.
247
patient. In the future, noninvasive imaging techniques may become the method of choice for diagnosis of thrombosis and embolism in patients with APS and other hypercoagulable states.
References [1] Asherson RA, Khamashta M, Ordi-Ros J, Derksen RHWM, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GRV. The ‘primary’ antiphospholipid syndrome: major clinical and serologic features. Medicine 1989; 68: 366–375. [2] Asherson RA. The catastrophic antiphospholipid syndrome. J Rheumatol 1992; 19: 508 – 512. [3] Asherson RA, Hughes GRV. Hypoadrenalism, Addison’s disease and antiphospholipid antibodies. J Rheumatol 1991; 18: 1–3. [4] Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993–997. [5] Provenzale JM, Ortel TL. Anatomic distribution of venous thrombosis in patients with antiphospholipid antibodies: imaging findings. AJR 1995; 165: 365 – 368. [6] Provenzale JM, Nelson RC, Ortel TL. Adrenal hemorrhage in patients with the primary antiphospholipid syndrome: imaging findings. AJR 1995; 165: 361 – 364. [7] Evans AJ, Sostman HD, Knelson MH, Spritzer CE, Newman GE, Paine SS, Beam CA. Detection of deep venous thrombosis: prospective comparison of MR imaging with contrast venography. AJR 1993; 161: 131 – 139. [8] Grist TM, Sostman HD, MacFall JR, Foo TK, Spritzer CE, Witty L, Newman GE, Debatin JF, Tapson V, Saltzman HA. Pulmonary angiography with MR imaging: preliminary clinical experience. Radiology 1993; 161: 131 – 139.
Case report
Disseminated thrombosis in primary antiphospholipid syndrome: MR findings James M. Provenzale a,*, Charles E. Spritzer a, Rendon C. Nelson a, Thomas L. Ortel b a
Department of Radiology, Box 3808, Duke Uni6ersity Medical Center, Durham, NC 27 710 -3808, USA b Department of Medicine, Duke Uni6ersity Medical Center, Durham, NC 27 710, USA Received 23 October 1996; received in revised form 3 December 1996; accepted 9 December 1996
Abstract We report the MR imaging findings in a patient with primary antiphospholipid syndrome, adrenal infarction and widespread thrombosis involving abdominal, pelvic, and pulmonary vessels. This syndrome should be suspected in patients with thromboses and organ infarctions of otherwise undetermined etiology. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Antiphospholipid antibody; Thrombosis; Pulmonary embolism; Adrenal hemorrhage
1. Introduction
2. Case report
The antiphospholipid syndrome (APS) consists of recurrent thromboses, cardiac valvular abnormalities, recurrent fetal loss, livedo reticularis (a purplish mottling of the skin due to vascular insufficiency) and thrombocytopenia [1]. APS occurs in patients with antiphospholipid antibodies, which are immunoglobulins that cross-react with phospholipids within cell membranes and are associated with a hypercoagulable state. The major types of antiphospholipid antibodies are the lupus anticoagulant and anticardiolipin antibodies [1]. APS can be seen in both systemic lupus erythematosus (SLE) patients (secondary APS) and patients who lack SLE features (primary APS) [1]. An APS-related thrombotic event typically involves only one vessel. Rarely, thrombosis can simultaneously involve multiple vessels, sometimes accompanied by organ infarction [2]. We report such a patient in whom simultaneous involvement of multiple vessels and organs was shown by MR imaging.
A 27-year-old man developed left leg deep venous thrombosis (DVT) that was successfully treated with intravenous heparin followed by oral warfarin for 1 year. Family history was notable for a paternal uncle and paternal grandfather who died at ages 45 and 38 years, respectively, with ill-defined disorders of hypercoagulability. At age 34 years, the patient developed right leg DVT which was again treated with anticoagulant therapy. He was also noted to be thrombocytopenic but a lupus anticoagulant was reportedly not identified. Subsequently, he developed chronic venous stasis changes and poorly healing leg ulcers. A prolonged activated partial thromboplastin time (\150 s; normal, B 23.6–37.1 s) that did not correct with mix, suggestive of the presence of a lupus anticoagulant, and a markedly elevated lgG anticardiolipin antibody titer (2110 gpl; normal, B 16 gpl) were found. At the age of 38 years, he developed left external iliac vein occlusion despite warfarin therapy with an international normalized ratio (INR) of 4.7 (the INR is a normalization factor for the protime that uses a correction factor for
* Corresponding author. Tel.: +1 919 6847409; fax: + 1 919 6847138.
0720-048X/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S 0 7 2 0 - 0 4 8 X ( 9 6 ) 0 1 1 5 4 - 0
J.M. Pro6enzale et al. / European Journal of Radiology 26 (1998) 244–247
different sensitivities of reagents to factor VII so that protimes from different laboratories can be compared. An INR of 2.0–3.0 usually proves adequate in normal individuals). He was treated with therapeutic subcutaneous heparin for 6 months and warfarin was then restarted with the therapeutic goal of keeping his factor II level below 30%. One month later he developed left flank pain, nausea and diaphoresis. Contrast-enhanced abdominal CT showed mild stranding of the left perinephric fat with a normal adrenal gland and kidney. Numerous venous collateral channels were seen comprised of enlarged inferior mesenteric, ascending lumbar and subcutaneous veins. Ventilation/perfusion lung scan showed perfusion defects in the left lower lobe without ventilation defects, consistent with pulmonary emboli and thought to be the source of the patient’s left flank pain. The patient developed right upper quadrant pain 2 days later. A new right adrenal mass was seen at abdominal sonography that correlated on MR imaging with an inhomogeneous mass having regions of hyperintense and hypointense signal intensity relative to liver on unenhanced T1-weighted and T2-weighted images, consistent with hemorrhage (Fig. 1A). Adrenal insufficiency was documented by low serum cortisol levels (1 mcg/dl) and an abnormal cortrosyn stimulation test. Gradient echo images of the pelvis showed bilateral common femoral vein thrombosis, left common iliac vein occlusion and a small right common iliac vein (Fig. 1B) with collateral flow through enlarged inferior mesenteric, ascending lumbar and subcutaneous veins (Fig. 1C). Gradient echo images of the pulmonary vasculature showed a filling defect in the left pulmonary artery, consistent with a pulmonary embolus (Fig. 1D), confirmed at catheter angiography (Fig. 1E). Because both common femoral veins were thrombosed, pulmonary angiography was performed via the right jugular vein, which subsequently thrombosed during the next 24 h. Intravenous heparin therapy was started in an attempt to treat pulmonary embolism and prevent further thromboses. During a 2 month follow-up period, no new thrombotic events have occurred.
245
3. Discussion There is increasing evidence that antiphospholipid antibodies are associated with a hypercoagulable state that can result in recurrent thromboses and infarction of brain and other organs [1,3,4]. Our patient had major features of primary APS, i.e. unexplained thromboses in the presence of antiphospholipid antibodies and without clinical or laboratory features of SLE. The finding of collateral venous circulation within the abdomen and pelvis was evidence of longstanding venous occlusive disease. These vascular occlusions occurred despite a degree of anti-coagulation that would be therapeutic for individuals without a hypercoagulable state. The development of pulmonary embolism and jugular vein thrombosis while on warfarin therapy was further evidence of a hypercoagulable state. DVT of the legs is the most common form of venous thrombosis in APS patients and is often accompanied by pulmonary embolism. However, thrombosis of the deep veins of the thorax, neck, abdomen (as in our patient) and dural sinuses have also been reported [5]. Arterial thromboses in APS patients usually occur in the peripheral arteries but can be seen in virtually any arterial bed, most notably in arteries supplying the brain, kidneys and viscera. Our patient experienced multiple, nearly simultaneous, thromboses and infarctions. The complications in our patient were more severe than routinely seen in APS. However, even more widespread simultaneous thromboses can rarely occur, causing infarction of brain, kidneys and other organs, often resulting in death (so-called catastrophic APS) [2]. Adrenal hemorrhage, frequently bilateral, is an uncommon, but potentially lethal complication of APS [3,6]. Adrenal hemorrhage or infarction should be suspected in an APS patient with abdominal pain and evidence of adrenal insufficiency. The cause of adrenal hemorrhage in APS patients is not known with certainty and may differ between individuals. Adrenal vein thrombosis has been postulated as the precipitating event of adrenal hemorrhage in some APS patients [3]. Therefore, adrenal hemorrhage may be another mani-
Fig. 1. A 39-year-old man with antiphospholipid antibodies, a history of multiple DVTs and external iliac vein occlusion and new left flank pain followed 2 days later by right upper quadrant pain. (a) Unenhanced T1-weighted spin-echo (550/20/2 (TR/TE/excitations)) MR image (top) and T2-weighted (2200/80/1) MR image (bottom) in the axial plane shows large inhomogeneous mass involving the right adrenal gland (arrows) with regions of hyperintense and hypointense signal intensity relative to liver consistent with hemorrhage. The left adrenal gland has a normal appearance. CT performed 10 days earlier (not shown) showed a normal right adrenal gland. (b) Gradient echo (33/13/1/60° (flip angle)) MR image of the pelvis in the axial plane shows normal signal intensity within common iliac arteries (solid arrows). No signal is present in the expected location of left common iliac vein, consistent with iliac vein occlusion. A small right common iliac vein is seen (arrowhead). On lower images, no flow was seen within the right external iliac vein. Flow is seen within an enlarged inferior mesenteric vein (curved arrow). Collateral veins (open arrows) are seen within subcutaneous fat. (c) Gradient echo (33/13/1/60°) image of the lower abdomen in the axial plane shows enlarged ascending lumbar veins (arrow) and inferior mesenteric vein (arrowheads). Normal signal intensity is seen in the inferior vena cava (curved arrow). (d) Gradient echo (33/13/1/60°) MR image of the chest in the axial plane shows a region of decreased signal intensity in the left pulmonary artery (arrow) consistent with pulmonary embolism. (e) Catheter angiogram of left pulmonary artery shows multiple intraluminal filling defects (arrowheads) due to pulmonary emboli.
246
J.M. Pro6enzale et al. / European Journal of Radiology 26 (1998) 244–247
Fig. 1.
J.M. Pro6enzale et al. / European Journal of Radiology 26 (1998) 244–247
festation of the hypercoagulable state in our patient. However, like some other previously reported APS patients with adrenal hemorrhage [6], the hemorrhage in our patient occurred while on anticoagulant therapy, raising the possibility that adrenal hemorrhage is a complication of warfarin therapy in some cases. The risk of recurrent thrombosis in APS is high and there is evidence to suggest that many APS patients require higher doses of anti-coagulation (INR\ 3.O) than individuals without a hypercoagulable state [4]. Such was the case in our patient in whom recurrent thrombosis occurred despite an INR of 4.7. Adrenal hemorrhage is not a contraindication to restarting anticoagulant therapy. Previous reports have documented APS patients with adrenal hemorrhage who have resumed anticoagulant therapy without complication [6]. The hazards of vessel catheterization during a period of pronounced hypercoaguablility in our patient are underscored by development of jugular vein thrombosis following pulmonary angiography. However, MR imaging demonstrated all of the important APS complications of our patient in a noninvasive manner. MR imaging has been shown to be accurate in diagnosing venous thrombosis, with the veins of the thorax, abdomen and extremities being readily assessed without the use of intravenous contrast agents [7]. More recently, MR imaging has shown promise as a noninvasive technique for detection of PE [8], as was also shown in our
.
247
patient. In the future, noninvasive imaging techniques may become the method of choice for diagnosis of thrombosis and embolism in patients with APS and other hypercoagulable states.
References [1] Asherson RA, Khamashta M, Ordi-Ros J, Derksen RHWM, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GRV. The ‘primary’ antiphospholipid syndrome: major clinical and serologic features. Medicine 1989; 68: 366–375. [2] Asherson RA. The catastrophic antiphospholipid syndrome. J Rheumatol 1992; 19: 508 – 512. [3] Asherson RA, Hughes GRV. Hypoadrenalism, Addison’s disease and antiphospholipid antibodies. J Rheumatol 1991; 18: 1–3. [4] Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993–997. [5] Provenzale JM, Ortel TL. Anatomic distribution of venous thrombosis in patients with antiphospholipid antibodies: imaging findings. AJR 1995; 165: 365 – 368. [6] Provenzale JM, Nelson RC, Ortel TL. Adrenal hemorrhage in patients with the primary antiphospholipid syndrome: imaging findings. AJR 1995; 165: 361 – 364. [7] Evans AJ, Sostman HD, Knelson MH, Spritzer CE, Newman GE, Paine SS, Beam CA. Detection of deep venous thrombosis: prospective comparison of MR imaging with contrast venography. AJR 1993; 161: 131 – 139. [8] Grist TM, Sostman HD, MacFall JR, Foo TK, Spritzer CE, Witty L, Newman GE, Debatin JF, Tapson V, Saltzman HA. Pulmonary angiography with MR imaging: preliminary clinical experience. Radiology 1993; 161: 131 – 139.