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Table of Contents
Year : 2022  |  Volume : 12  |  Issue : 3  |  Page : 83-88

Multiple arterial thrombosis

Department of Cardiology, SDM Narayana Heart Centre, SDM Medical College, Dharwad, Karnataka, India

Date of Submission02-Jul-2020
Date of Decision12-Aug-2020
Date of Acceptance14-Jul-2022
Date of Web Publication14-Sep-2022

Correspondence Address:
Dr. Sagar Mali
Department of Cardiology, SDM Narayana Heart Centre, SDM Medical College, Sattur, Dharwad - 580 009, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JICC.JICC_48_20

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Bleeding following any injury is due to damaged blood vessel and is usually kept in check by a process called hemostasis. At times, this process may be abnormally affected by pathological factors or causes subsequently leading to thrombus formation and occlusion of blood vessels. It can affect either arteries or veins. The events in the pathogenesis of thrombosis occur in a vicious cycle. We report a case of 38-year-old male with multiple arterial thrombosis involving brachial artery, common carotid artery, and main pulmonary artery. He had raised hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin on presentation. He was successfully treated with injection alteplase (recombinant tissue plasminogen activator), injection enoxaparin, and dual oral antiplatelet therapy.

Keywords: Coronavirus disease 2019 and thrombosis, multiple arterial thrombosis, venous thromboembolism

How to cite this article:
Shakapur C, Mali S. Multiple arterial thrombosis. J Indian coll cardiol 2022;12:83-8

How to cite this URL:
Shakapur C, Mali S. Multiple arterial thrombosis. J Indian coll cardiol [serial online] 2022 [cited 2023 Feb 8];12:83-8. Available from: https://www.joicc.org/text.asp?2022/12/3/83/356067

  Introduction Top

The major pathological event behind abnormal hemostasis and thrombosis is endothelial dysfunction. It leads to increase in adhesion molecules on inflammatory cells.[1],[2],[3] Such activated inflammatory cells release cytokine and chemokines, causing endothelial activation and release of growth factors causing growth of vascular smooth muscle cells.[4] Both these events lead to release of multiple factors from activated endothelial and vascular smooth muscle cells causing activation of platelets and coagulation-fibrinolysis system.[5],[6],[7] The secreted factors act on the cells by which they are secreted and also acts in the vicinity of the secreting cells.[8],[9] Various secreted vasoactive factors have continuous and excessive effect on Rho-kinase system producing large number of reactive oxygen species (ROS).[10],[11],[12] In turn, these ROS produce excessive oxidative stress and further endothelial dysfunction.[13] Some other abnormal effects of these ROS are as follows:

  1. Upregulated and enhanced expression of adhesion molecules
  2. Activation of platelets
  3. Activation of the coagulation system.[9],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24]

The common complications of arterial thrombosis are myocardial infarction (MI) and stroke[25],[26] whereas venous thrombosis (VT) causes venous thromboembolism (VTE), i.e., deep VT (DVT) and pulmonary embolism.[27],[28] A pathological examination of thrombus can easily distinguish arterial thrombus from venous thrombus. In arterial thrombi, large numbers of platelet aggregates are seen around ruptured atherosclerotic plaques, whereas venous thrombi are predominantly formed by combination of fibrin and red blood cells in addition to platelets in a probably intact venous drainage system.

  Arterial Thrombosis Top

Normally endothelial cells secrete nitric oxide (NO) and prostacyclin, which decides clot size. These cells also carry CD39 and CD79, enzymes that hydrolyze ADP to AMP and AMP to adenosine, respectively. Adenosine thus formed prevents platelet activation and aggregation. It also acts as anti-inflammatory mediator.[29] At the site of atherosclerotic plaque, ability of endothelial cells to secrete NO and prostacyclins is compromised, unabling them to regulate thrombotic propagation.[29],[30]

The prevalence of angina and no obstructive coronary arteries and MI and no obstructive coronary arteries has been increasing in recent years. In these cases, though exact underlying mechanism is unclear, it has been proposed that arterial thrombosis does not occur due to plaque rupture.[31] Platelets play a crucial role in arterial thrombosis. Platelets and activated endothelial cells secrete protein disulfide isomerases (PDIs). These PDIs initiate thrombus formation by reacting with ROS and NO.[32],[33],[34] PDIs also cause platelet aggregation,[35] by activation of tissue factor (TF) and increasing fibrin production.[33] This leads to rapid thrombus formation on the surface of activated platelets.[36] Furthermore, binding of ADP to P2Y1, P2Y12 receptors and thrombaxane A2 to thrombaxane receptor initiates platelet aggregation.[37],[38] Therefore, use of antiplatelet agents such as clopidogrel, prasugrel, acetylsalicylic acid, and ticagrelor has been successfully used in arterial thrombolytic therapy.[39],[40]

Various risk factors implicated in arterial thrombosis are smoking, hypertension, diabetes, high levels of low-density lipoprotein-cholesterol, chemotherapeutics,[41] infection,[42],[43] high von Willebrand factor (vWF) in plasma, low level of a disintegrin and metalloprotease with thrombospondin type 1 repeats 13,[44] pregnancy, stillbirths, repeated abortions,[45] SLE,[46],[47] hormone therapy,[48],[49],[50] and hereditary thrombophilia.[51] Like platelets, vWF also plays a crucial role in platelet adhesion. It is a glycoprotein synthesized by endothelial cells and megakaryocytes. It is stored in Weibel–Palade bodies of endothelial cells and α-granules of platelets. vWF binds glycoprotein Ibα and αIIbβ3 of platelets to subendothelial collagens whenever subendothelial matrix proteins are exposed due to arterial injury. Furthermore, binding of glycoprotein VI and α2 β1 of platelets with collagen activates platelets and forms thrombus through adhesion and spreading.[52],[53],[54],[55],[56],[57],[58],[58]

  Venous Thromboembolism Top

It includes DVT and pulmonary thromboembolism (PTE).[27],[28] Autophagy (regulate vWF secretion) and inflammation (increases surface selectin expression) can activate venous endothelium.[48],[59] Activated endothelial surface promotes attachment of platelets and leukocytes. Leukocyte gets activated upon attachment and initiates a coagulation cascade through expression of TF. TF can activate extrinsic coagulation system and lead to either arterial thrombosis or VT or both. Venous stasis or low blood flow is another factor responsible for VTE. It causes hypoxia, leading to increased expression of endothelial adhesion molecules. This further leads to leukocyte attachment and vicious cycle continues.[48] Erythrocytes also play a role in thrombosis by allowing compact packaging due to their biconcave shape, which is resistant to fibrinolysis.[60]

Hospitalized patients are at higher risk of developing DVT. DVT can lead to PTE. PTE is a life-threatening manifestation of VTE, which has high recurrence rate after stopping anticoagulation therapy.[61] Various risk factors for thromboembolism are aging, trauma, obesity,[41] infection,[42] genetic conditions, drugs, pregnancy, malignancy,[62] hormonal contraception,[63] elevated D-diamer after stopping anticoagulation agents, antithrombin, antiphospholipid syndrome, low protein C and S,[61] anemia,[48] genetic mutations,[48],[64] non-O blood group,[65] elevated mean platelet volume,[66] and posttraumatic stress disorder and trauma exposure in women.[67]

The current pandemic of coronavirus disease 2019 (COVID-19) is known to produce thrombotic events through severe infection, excessive inflammation, immobilization, and hypoxia.[68],[69],[70] Early reports have shown patients suffering from COVID-19 infection developed DIC (disseminated intravascular coagulation).[71],[72] COVID-19 infection causes increase in the levels of lactate dehydrogenase, C-reactive protein, ferritin, D-dimer and interleukin 6 (IL 6).[73] IL 6 has procoagulant effect and its levels are used to monitor disease severity.[74] Severely ill patients had variable levels of increased prothrombin time (PT), INR[73],[75],[76] and thrombin time. Study by Tang et al. showed 21 (11.5%) patients who died of COVID-19 had raised levels of fibrin degradation products and D-dimer as well as prolonged PT.[71],[77] Such hemostatic changes in COVID-19-infected patients suggest some form of coagulopathy predispose these patients to thrombotic events. We do not know whether these hemostatic changes are direct effect of COVID-19 infection or secondary to cytokine storm (observed during COVID-19 and few viral infections).[78],[79],[80],[81] Furthermore, these hemostatic changes could be secondary to liver dysfunction.[82] Oxley et al. presented a case series of COVID-19 patients younger than 50 years who had large-vessel ischemic stroke.[83] Klok et al. studied 184 COVID-19 pneumonia patients and found VTE (in 27% of patients) and arterial thrombotic events (in 3.7% of patients). They recorded 31% incidence rate of thrombotic complications in COVID-19 infection and recommended thrombosis prophylaxis in all intensive care unit admitted COVID-19 patients.[84]

  Case Report Top

A 38-year-old male was referred from surgery to cardiac outpatient department with complaints of bluish discoloration of fourth and fifth finger of right arm and acute right upper limb pain of 8 days duration. Pain was continuous and exacerbated on exertion in the right upper and lower arm but he could perform daily activities. There was no history of trauma. He was tobacco chewer for last 10 years. He did not have any comorbidities such as hypertension, diabetes, thyroid disorder, or history of cardiovascular disease.

On examination, his right hand had signs of ischemia with bluish discoloration of 4th and 5th finger, coldness, and capillary refilling was slow. There was no muscle wasting in the hand and both sensation and movements were intact. The muscles of forearm and arm were non tender. On the right side, brachial artery pulse was palpable, but no pulse was palpable beyond that point. On the left side, all peripheral pulses were palpable. His left common carotid pulse was also not palpable.

Arterial Doppler study of the right upper limb showed echogenic thrombus in the lower third segment of the brachial artery. The thrombus was seen extending into the proximal 1/3rd segment of ulnar artery. Rest of the ulnar and radial arteries showed severely reduced flow velocities at parvus tardus wave form. Arterial Doppler study of the left upper limb was normal. Arterial Doppler study of the neck showed maximum intima-media thickness of 0.9 mm in bilateral common carotid arteries. On the left side, common carotid artery had hypoechoic thrombosis in its entire length extending into the external carotid artery. Left internal carotid artery had patent lumen with low flow velocities (40–50 cm/s). Rest of the study on the right side of the neck was normal. Bilateral vertebral arteries were also normal.

His computed tomography (CT) and angiography showed thrombosis in distal right brachial artery (3.5 cm), proximal and midportion of the right ulnar artery (8 cm). There was near complete occlusion of left common carotid artery, external carotid and proximal portion of internal carotid artery noted during the imaging [Figure 1]. CT angiography also revealed saddle-shaped thrombus at the bifurcation of main pulmonary artery with thrombus extending into the right and left main pulmonary arteries, suggesting acute PTE [Figure 2].
Figure 1: Computed tomography angiography showing complete occlusion of left common carotid artery due to thrombus in a 38-year-old male

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Figure 2: Extensive acute central pulmonary thrombus extending into both central pulmonary arteries in a 38-year-old male

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His electrocardiograph and 2D echo study did not show any abnormal findings. Blood investigation reports are shown in [Table 1].
Table 1: Complete blood count report

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  Discussion Top

In our case, the patient had raised levels of hemoglobin, hematocrit, and mean corpuscular volume (MCV) and mean corpuscular hemoglobin. The patient was given injection alteplase (recombinant tissue plasminogen activator) 90 mg intravenously as continuous infusion over 2 h after 10 mg intravenous bolus dose. He was started on injection enoxaparin 60 mg subcutaneously twice daily for 5 days along with oral clopidogrel (75 mg BD) and aspirin (75 mg OD). The patient was discharged in stable condition with advice of oral acenocoumarol (3 mg OD) and combination of aspirin + atorvastatin (75/10 mg OD).

A study by Rezende et al. showed that high MCV (above 101.1 fL) has strong association with VT.[85] Various studies have shown that high hematocrit levels are associated with higher risk of arterial thrombosis[86],[87],[88],[89],[90],[91],[92],[93] as well as VT.[94],[95],[96],[97],[98] The underlying mechanism could be increased blood viscosity (due to increased hematocrit) which increases residence time of circulating clotting factors and platelets in the vicinity of dysfunctional endothelium.[99] The movement of platelets toward the vessel wall is also promoted by increased blood viscosity, thus predisposing to interaction with vasculature and subsequent clotting.[100] Increases in the hematocrit and blood viscosity also predispose to the low-flow conditions and change in shear rate, thereby decreasing velocity gradient and promoting blood clotting.[99],[101]


We would like to thank Dr Vivekanand Gejapati, Head of Department, Cardiology, for his expert advice and encouragement. We would also like to thank Dr. Kirti L for her support.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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