The CLOT storm: Hypercoagulable Condition Causing Acute Limb Ischemia

Author: The Medical City Vascular CRF Lea Farrah D. Abella, MD

A 41-year-old female with no co-morbidities presented with a 3-day history of worsening right leg pain, swelling, mottling, and numbness. Two years prior, she had experienced intermittent bilateral leg pain during ambulation,initially diagnosed as lumbar radiculopathy. However, despite completing physical therapy, her symptom persisted. During this admission, her symptoms became more severe, with associated swelling, claudication, and increasing pain, ultimately prompting her to seek medical attention. Physical examination revealed significant ischemia in the right lower extremity, including absent pulses, mottling, poikilothermia, and impaired sensation.

The patient’s medical history included long-term use of oral contraceptives (Yasmin) for over a decade, and she denied any recent trauma or injury. The patient also has a history of two miscarriages: one at 10 weeks of gestation and another at 12 weeks of gestation. The patient's lab results and imaging studies (CT angiogram) confirmed the presence of thrombotic occlusions in multiple arterial segments, including the infrarenal abdominal aorta, bilateral external iliac arteries, and both femoral and tibial arteries.

CT Aortogram

Fig 1: A soft tissue thrombus is seen causing severe to total occlusion with no contrast flow at the infrarenal abdominal aorta at the level of L2 vertebra.

CT Peripheral Angiogram

Fig 2: Occluded right common femoral, superficial and deep femoral, popliteal, peroneal, anterior and posterior tibial as well as the right dorsalis pedis arteries due to an acute thrombus with faint opacification

from the right Superficial femoral artery from the collateral flow.

There is a long segment total occlusion pointed by the yellow arrow due to thrombosis seen starting in the lower proximal left superficial femoral artery down to its distal segment with collateral flow to the popliteal artery via patent left deep femoral artery and its branches.

The patient was started on a heparin drip for anticoagulation, and underwent emergent open thrombectomy to remove the thrombus from the affected arterial segments.

Fig 3: Whitish thrombus associated with chronic stages of thrombosis from the left common, deep and superficial femoral arteries. Dark red thrombus from the right infrarenal aorta and from the right distal external iliac artery indicating acute stages of arterial thrombosis.

Post-procedure, the patient was closely monitored in the intensive care unit (ICU), where she was given antibiotics and continued on heparin. A repeat CT angiogram showed no significant progression of ischemia. Given the patient’s improvement, the management plan shifted to medical management with ongoing anticoagulation and surveillance, including a repeat arterial duplex scan in 3 months. The patient was advised to pursue further workup for hypercoagulable conditions and autoimmune disorders especially Anti-phospholipid Antibody Syndrome, although financial constraints limited this aspect of her care. Patient was then sent home with Warfarin 5mg tab once a day to target a Protime INR of 2-3.

DISCUSSION:

Arterial thrombotic events causing Acute Limb Ischemia (ALI) in the younger population as our patient, without a readily apparent etiology present significant diagnostic and management challenge. Given that the patient has no known co-morbidities with a history of 2 miscarriages, a possibility of a an Antiphospholipid Antibody Syndrome (APAS) as the etiology of this case was considered.

The association between inherited thrombotic disorders and arterial thrombosis is not well characterized. Given the rarity of the stronger inherited thrombophilias and their questionable role in arterial thrombosis formation, Guidelines only consider testing after extensive evaluation for other causes in younger patients (younger than 50- 55 years), particularly if there is a family history of venous or arterial thrombosis. 2 The most common acquired thrombophilia is Antiphospholipid syndrome (APS) or Hughes’s Syndrome which is an acquired thrombophilia with a well-documented risk of arterial thrombosis. 2 The clinical criteria for the diagnosis of the condition encompass both vascular (venous or arterial) thrombosis and pregnancy morbidity which the patient fulfilled both. Pregnancy-related complications include fetal death after 10 weeks of gestation, premature birth at or before 34 weeks due to preeclampsia, three or more consecutive abortions at or before 10 weeks, and placental insufficiency occurring before 34 weeks of gestation. Laboratory criteria involve the presence of specific antibodies, including anticardiolipin antibodies (either IgG or IgM), anti-β2-glycoprotein I antibodies (IgG or IgM) exceeding the 99th percentile, and the lupus anticoagulant antibody. These laboratory criteria must be confirmed on two or more occasions, at least 12 weeks apart. These clinical and laboratory markers are used to assess and diagnose the condition, which is often associated with thrombosis and adverse pregnancy outcomes. If this was a case of APAS, her concomitant chronic use of an oral contraceptive pill increases the odds of thrombosis by 4 to 6 times or more. 4 When managing antiphospholipid syndrome (APAS) with arterial thrombosis, treatment with vitamin K antagonists (VKA) is generally recommended. The target International Normalized Ratio (INR) for VKA therapy should typically range between 2–3 or 3–4, depending on the individual’s risk of bleeding and recurrent thrombosis. In some cases, combining VKA with low dose Aspirin (LDA) may also be considered. The current evidence suggests that DOACs are unsuitable for patients with definite APS and arterial thrombosis due to the high risk of recurrent thrombosis. For patients who experience

recurrent arterial thrombosis despite adequate VKA treatment, it may be necessary to increase the INR target to 3–4, add LDA, or switch to low molecular weight heparin (LMWH), after thoroughly evaluating for other potential causes of the thrombosis.1 References:

1. European League Against Rheumatism. EULAR Recommendations for the Management of

Antiphospholipid Syndrome. Annals of the Rheumatic Diseases, vol. 78, no. 9, 2019, pp. 1296-1304

2. Miyakis, Shigeki, et al. "International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome (APS)." Journal of Thrombosis and Haemostasis, vol. 4, no. 2, 2006, pp. 295-306

3. Weinberg, Ira, and Michael R. Jaff. "Nonatherosclerotic Arterial Disorders of the Lower Extremities." Circulation, vol. 126, no. 2, 2012, pp. 213-222

4. Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. BMJ 1968; i: 199–205.