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Thrombosis
Thromboses
Thrombosis is the formation of a blood clot within the vascular system, frequently causing obstruction. There are two forms of thrombosis, venous thrombosis and arterial thrombosis. German physician Rudolf Virchow first postulated, that a triad of conditions predispose to thrombus formation, these three factors being abnormalities in the vessel wall, blood flow and the coagulability of blood. The lesion and the syndrome produced by the thrombus depend on its location and size.

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WIKIDATA, CC BY-SA 4.0

Presentation

Clinical presentation depends on type of vessel and organ involved and associated embolism. Cases of deep venous thrombosis (DVT) present with swelling of leg, discoloration of leg and pain. Cases of pulmonary embolism often are secondary to deep venous thrombosis and present with acute chest pain, dyspnea, cough, and hemoptysis.

Embolus in internal carotids, vertebral arteries and circle of Willis presents with recurrent dizziness, confusion, limb weakness, sensory dysfunction, speech disorders, facial asymmetry, bladder dysfunction and abnormal gait. Thromboembolic complications in the heart presents with severe chest pain, sweating, palpitation, anxiety and syncope. Portal vein thrombosis may cause adnominal distension, pain in abdomen and breathing difficulty. Jugular vein thrombosis causes fever, neck swelling, and cervical pain [6].

Entire Body System

  • Pain

    Jugular vein thrombosis causes fever, neck swelling, and cervical pain. [symptoma.com]

    If you still have pain you can take paracetamol or ibuprofen. As well, try not to load your foot a lot until discomfort has disappeared. [trombo.info]

    Pain and swelling in the leg are common symptoms. Post-thrombotic syndrome may also happen following deep vein thrombosis of a leg vein. It is a long-term problem with pain, swelling, and redness. [saintlukeskc.org]

    This report describes a case of spontaneous IJV thrombosis leading to neck pain and swelling as a primary manifestation of antiphospholipid (Hughes) syndrome. [ncbi.nlm.nih.gov]

  • Weakness

    Call an ambulance or go to the emergency department if: you have chest pain you cough up blood you are short of breath you feel faint or pass out you are nauseous or vomiting you are numb and weak down one side, or there is a weakness in your face you [healthdirect.gov.au]

    PATIENT CONCERNS: A 59-year-old Korean woman patient with hypertension was admitted due to dysarthria and left side motor weakness. [ncbi.nlm.nih.gov]

    Testing may be considered in younger patients with weak provoking factors, a strong family history, or recurrence at a young age. [nejm.org]

    The symptoms of a stroke can come on suddenly and may include: numbness or weakness down one side, ranging in severity from weakness in your hand to complete paralysis of the whole side of your body weakness in your face, which can make you drool saliva [nhsinform.scot]

    Embolus in internal carotids, vertebral arteries and circle of Willis presents with recurrent dizziness, confusion, limb weakness, sensory dysfunction, speech disorders, facial asymmetry, bladder dysfunction and abnormal gait. [symptoma.com]

  • Leg Swelling

    However, they are sometimes considered in people with massive leg clots to prevent long-term leg swelling and pain (called post-phlebitis syndrome). [health.harvard.edu]

    Symptoms and Signs of Deep Vein Thrombosis (Blood Clot in Leg) Swelling, usually in one leg Leg pain or tenderness Reddish or bluish skin discoloration Leg warm to touch The symptoms of a blood clot may feel similar to a pulled muscle or a “Charlie horse [stoptheclot.org]

    Wear elastic compression stockings: If you have a history of blood clots or leg swelling, elastic stockings reduce leg swelling and the chance of blood clots. The stockings must be worn snugly to offer support while ensuring adequate circulation. [lifebridgehealth.org]

    This condition is characterized by pooling of blood, chronic leg swelling, increased pressure, increased pigmentation or discoloration of the skin, and leg ulcers known as venous stasis ulcers. [my.clevelandclinic.org]

  • Gangrene

    Examinations after death have shown that thrombosis exists for some distance around the gangrenous mass. Thrombosis of the subclavian and axillary veins is much less frequent. [thesaurus.com]

    Venous gangrene may result. Infection rarely develops in venous clots. [merckmanuals.com]

    Gas gangrene. Investigations [ 6 ] Ultrasound (compression with either Doppler or colour Doppler) is recommended as the investigation of choice. [patient.info]

    Can also get microangiopathic hemolytic anemias like TTP/HUS, HELLP, and in Catastrophic APS (see below) Skin manifestations are common and include splinter hemorrhages, livedo reticularis, skin necrosis/infarction and digital gangrene. [errolozdalga.com]

    Endovascular treatment of phlegmasia cerulea dolens with impending venous gangrene: manual aspiration thrombectomy as the first-line thrombus removal method. Cardiovasc Intervent Radiol 2011;34:1214-21. Kahn SR. [acc.org]

  • Acute Onset of Symptoms

    Overall accuracy 90% to 100%, depending on vein or sinus Echoplanar T2 susceptibility-weighted imaging combined with MRV are considered the most sensitive sequences Practical application Acute onset of symptoms Acute or subacute onset of symptoms Emergency [stroke.ahajournals.org]

Gastrointestinal

  • Vomiting

    Our patient presented almost 1 month after an episode of sudden-onset severe holocranial headache associated with vomiting that had resolved completely within 2 days. He was neurologically intact at the time of presentation. [ncbi.nlm.nih.gov]

    […] dysplasia, cervix 654.6 early onset of delivery (spontaneous) 644.2 eclampsia, eclamptic (coma) (convulsions) (delirium) (nephritis) (uremia) 642.6 edema 646.1 effusion, amniotic fluid 658.1 embolism emesis (gravidarum) - see Pregnancy, complicated, vomiting [icd9data.com]

    Call an ambulance or go to the emergency department if: you have chest pain you cough up blood you are short of breath you feel faint or pass out you are nauseous or vomiting you are numb and weak down one side, or there is a weakness in your face you [healthdirect.gov.au]

    Signs of excessive bleeding can include prolonged nose bleeds, severe bruising, bleeding gums, vomiting or coughing up blood, and, for women, increased bleeding during menstruation. [natfonline.org]

    People then vomit blood. The blood may also pass through the digestive tract, making stools black, tarry, and foul-smelling (called melena). [merckmanuals.com]

  • Hematochezia

    Because of the ongoing hematochezia, after successful revascularization of the culprit vessel, the patient was medicated with Clopidogrel, in place of one of the more powerful new oral P2Y12 inhibitors that currently represent the gold standard therapy [ncbi.nlm.nih.gov]

Liver, Gall & Pancreas

  • Protein S Deficiency

    Protein S deficiency or dysfunction -- Protein S is a cofactor with Protein C Prothrombin 20210 mutation -- a mutation that results in an increased amount of thrombin (activated factor II) in the circulation, which is associated with an increased risk [web.archive.org]

    protein deficiencies (antithrombin III, protein C, and protein S) as risk factors for CVT. [stroke.ahajournals.org]

    Protein C deficiency Protein S deficiency Prothrombin 20210A mutation Factor V Leiden Dysfibrinogenemias and disorders of plasminogen activation Intravenous (IV) drug abuse Oral contraceptives Estrogens Heparin-induced thrombocytopenia (HIT) Epidemiology [emedicine.medscape.com]

Eyes

  • Visual Impairment

    Visual Loss Severe visual loss due to CVT rarely occurs (2% to 4%). 55, 193, 235 Papilledema can cause transient visual impairment, and if prolonged, optic atrophy and blindness may ensue. [stroke.ahajournals.org]

Skin

  • Erythema

    References:[2][4][5] Clinical features May be asymptomatic Localized unilateral symptoms Typically affects deep veins of the legs, thighs, or pelvis Swelling, feeling of tightness or heaviness Warmth, erythema, and possibly livid discoloration Progressive [amboss.com]

    When present, symptoms and signs of DVT (eg, vague aching pain, tenderness along the distribution of the veins, edema, erythema) are nonspecific, vary in frequency and severity, and are similar in arms and legs. [merckmanuals.com]

    Physical exam may reveal a palpable cord, ipsilateral edema, erythema, or venous distension. Rarely, patients with DVT may present with evidence of arterial insufficiency due to massive iliofemoral DVT. [acc.org]

    Symptoms range from mild erythema and localized induration to massive extremity swelling and ulceration, usually exacerbated by standing and relieved by elevation of the extremity. [emedicine.medscape.com]

    Patients with deep vein thrombosis (DVT) often present with isolated extremity swelling, pain, warmth, and erythema at the site of the blockage. [ncbi.nlm.nih.gov]

Musculoskeletal

  • Leg Pain

    Symptoms Deep vein thrombosis signs and symptoms can include: Swelling in the affected leg. Rarely, there's swelling in both legs. Pain in your leg. The pain often starts in your calf and can feel like cramping or soreness. [mayoclinic.org]

    leg Red or discolored skin on your leg Veins that are swollen, red, hard, or tender to the touch you can see Call 911 or go to an emergency room right away if you notice leg pain or swelling and: Sudden coughing, which may bring up blood Sharp chest [webmd.com]

    Deep vein thrombosis in the right leg In some instances, there may be no symptoms, but deep vein thrombosis signs and symptoms may often include: swelling of the affected leg (less often, there could be swelling in both) a leg pain, which usually starts [leading-medicine-guide.com]

    Symptoms and Signs of Deep Vein Thrombosis (Blood Clot in Leg) Swelling, usually in one leg Leg pain or tenderness Reddish or bluish skin discoloration Leg warm to touch The symptoms of a blood clot may feel similar to a pulled muscle or a “Charlie horse [stoptheclot.org]

    pain, intractable oedema, leg ulcers) than DVT in non-pregnant women. 1 3 This article provides an update on the diagnosis and management of pregnant women with DVT. [bmj.com]

  • Leg Discoloration

    Symptoms: Swelling of leg, discoloration of leg, pain in leg, acute chess pain, breathlessness, cough, hemoptysis, dizziness, confusion, limb weakness, sensory dysfunction, speech disorders, facial asymmetry, bladder dysfunction, abnormal gait, sweating [symptoma.com]

Neurologic

  • Stroke

    […] nonpyogenic, with stroke Cerebrovascular accident due to nonpyogenic cerebral venous thrombosis 437.6 Excludes ICD-9-CM Volume 2 Index entries containing back-references to 437.6 : [icd9data.com]

    CONCLUSION: We found a short-term elevated risk of ischemic stroke after exposure to air pollution. These findings have public health implications for stroke prevention and emergency health services delivery. [ncbi.nlm.nih.gov]

    [citation needed] Stroke[edit] Acute thrombus in the right MCA M1 branch A stroke is the rapid decline of brain function due to a disturbance in the supply of blood to the brain. [en.wikipedia.org]

    Harvard Health Publishing: "Thrombotic Stroke." [webmd.com]

    Find out more about the symptoms of a heart attack Stroke Arterial thrombosis can cause a stroke if a blood clot is blocking an artery that supplies blood to your brain. [nhsinform.scot]

  • Headache

    6 53 M Subacute Headache, L paresis, general seizure 15 R hem SSS, CV Protein C deficiency 7 29 F Acute Headache, coma 6 No SSS, L and R LS, SS, CV, DVS OC 8 39 M Acute Headache, papilledema, aphasia, mental, R paresis 12 R and L hem SSS, L LS, SS, L [stroke.ahajournals.org]

    On neurological examination, she had no headache but presented with right facial paresis with dysarthria. Her right hemiparesis was present in the upper and lower extremities. [ncbi.nlm.nih.gov]

    Patient 2 A 46-year-old woman with a history of hypertension presented with 3 weeks of worsening headaches. [ajnr.org]

  • Seizure

    DVS OC 20 28 F Acute Headache, mental, L paresis, general seizure 14 R hem SSS, CV Puerperium 21 25 M Acute Headache, papilledema, mental, paresis, general seizure 11 R hem SSS, CV 22 37 F Acute Headache, papilledema, bilateral paresis, general seizure [stroke.ahajournals.org]

    Similar word related to Thrombosis are Occlusion, Seizure and Stroke. The antonyms of Thrombosis are Consciousness. For knowing how to pronounce Thrombosis can listen to it on this page. [urdupoint.com]

    A 10-year-old woman presented with seizure episodes. Angiographic evaluation revealed a collection of vessels draining into the superior sagittal sinus via the vein of Trolard, concerning for a DVA. [ncbi.nlm.nih.gov]

  • Confusion

    Embolus in internal carotids, vertebral arteries and circle of Willis presents with recurrent dizziness, confusion, limb weakness, sensory dysfunction, speech disorders, facial asymmetry, bladder dysfunction and abnormal gait. [symptoma.com]

    […] an ambulance or go to the emergency department if: you have chest pain you cough up blood you are short of breath you feel faint or pass out you are nauseous or vomiting you are numb and weak down one side, or there is a weakness in your face you are confused [healthdirect.gov.au]

    Stroke, which symptoms include sudden confusion, numbness or weakness of one side of the body, vision problems, and loss of balance, among others. [docdoc.com.sg]

    Filling defects should not be confused with Pacchionian bodies (arachnoid granulations) which can be seen in essentially all dural sinuses and are especially common in the superior sagittal sinus and transverse sinus. [radiopaedia.org]

    Bleeding in your brain can bring on severe headaches, vision changes, unnatural movements, and confusion. Call 911 or go to the emergency room if you notice any of these symptoms. [medicinenet.com]

  • Convulsions

    […] cervicitis (conditions classifiable to 616.0 ) 646.6 chloasma (gravidarum) 646.8 cholelithiasis 646.8 cholestasis 646.7 chorea (gravidarum) - see Eclampsia, pregnancy coagulation defect 649.3 conjoined twins 678.1 contraction, pelvis (general) 653.1 convulsions [icd9data.com]

Workup

Objective of workup is confirming obstruction of vessel lumen by imaging studies such as color Doppler for deep venous thrombosis and portal vein thrombosis, angiography in case of myocardial infarction or ischemia, CT scan and X-ray in case of jugular or carotid involvement. ECG, complete blood count (CBC), kidney function test, liver function test, urine examination and blood coagulation profile (PT, aPTT, INR), must be done to rule out complications and set baseline. Depending on complications other investigations like CSF or peritoneal fluid examination may be advised [7].

Serum

  • Hypercholesterolemia

    DIAGNOSES: Hypercholesterolemia, proteinuria, and elevated plasma creatinine level were present. [ncbi.nlm.nih.gov]

    The main mechanism is exposure of tissue factor to the blood coagulation system.[22] Inflammatory and other stimuli (such as hypercholesterolemia) can lead to changes in gene expression in endothelium producing to a pro-thrombotic state.[23] When this [en.wikipedia.org]

Treatment

Treatment is directed towards two aspects. Treatment of complication and treatment to dissolve as well prevent recurrence of thrombus. Treatment of complication like swelling and pain of leg in DVT are managed by stockings and NSAIDS. Myocardial ischemia/infarction with centrally acting analgesics, nitroglycerine and life support. Pulmonary thromboembolism with oxygen, and other life support, antibiotics.

Whatever is a complication, cornerstone of treatment is dissolving blood clot and prevent recurrence. Thrombolytic drugs like streptokinase or human tissue plasminogen activator are used to dissolve clot. For prevention of thrombus formation anticoagulants like heparin, warfarin, and dabigatran are used. Anticoagulant and thrombolytic therapy needs routine INR monitoring [8].

Prognosis

Mostly cases are detected upon symptoms or complications. If left untreated thrombosis causes significant morbidity and mortality due to cardiopulmonary complications like pulmonary thromboembolism, stroke or myocardial infarction. Complications are mostly prevented by anticoagulant therapy. Even after treatment in 33 percent of cases, the condition recurs [5].

Etiology

Thrombosis occurs as a result of altered pathophysiology between blood flow, protection of vessel wall by endothelium and blood composition. Regular blood flow prevents endothelial injuries and activation of coagulation pathway. This flow is altered in certain conditions like sedentary behavior, prolonged sitting or standing, occlusion of vessels by tumors, atrial or ventricular fibrillation, shock and heart failure [1].

In the endothelium if injured, connecting tissue containing collagen, is exposed to coagulation factor which activates coagulation pathway. Endothelial injury may be caused by uncontrolled blood pressure, stress, atheroma, infection and altered blood flow.

Hypercoagulability indicates altered composition of blood. It is mostly due to autoimmune conditions like deficiency of antithrombin, protein C or protein S or immunological conditions like antiphospholipid antibody syndrome [2].

Epidemiology

Annually 1 to 2 per thousand new cases are diagnosed in US. Incidence increases with age up to 1 per 100. Out of this 10 to 30 percent of diagnosed cases die within month of diagnosis. In 33 percent cases there is recurrence of condition in next 10 years. 5 to 8 percent of Americans have genetic predisposition for thrombosis. Incidence of thrombosis increases with age, weight, sedentary lifestyle, smoking and stress [3].

Pathophysiology

Injury to blood vessel causes exposure to tissue factor or collagen in vessel walls depending on nature of injury. In both cases it activates platelets and forms a platelet plug. Activated platelets along with tissue factor and collagen in vessel wall initiate a cascade of actions known as coagulation pathway which may be intrinsic or extrinsic depending on etiology. This leads to initiation and formation of plug of platelets enmeshed in fibrin thread. This plug if large in size causes diminution of vessel lumen size resulting in either decreasing blood flow if vessel is vein and diminished blood supply to tissues if vessel is artery.

Accordingly thrombosis is classified as arterial or venous. Arterial thrombosis causes decreased blood supply to supplying tissue resulting in ischemia or infarct [4]. Examples are stroke, myocardial infarction and limb ischemia. Venous thrombosis causes stagnant blood flow in backward direction of flow and edema of distal part of body where it is occluded. Examples are jugular vein thrombosis, cerebral venous sinus thrombosis, Budd-Chiari syndrome and Paget-Schroetter disease.

Prevention

Since many risk factors for thrombosis are modifiable, prevention of thrombosis is possible. This includes weight reduction, exercise, diet control, smoking cessation, stopping hormonal contraceptive and control of blood pressure. Once condition is developed, anticoagulant therapy will be added to this list of factors for prevention of recurrence [9].

Summary

Formation of clot within vessel wall is called thrombosis. Thrombosis cause stagnancy of blood flow within vessels by narrowing the lumen which may precipitate edema if vein is involved or ischemia of tissue if artery is involved. Clot may dislodge from its original position leading to embolism in organ where it is lodged.

Symptoms and sign of thrombosis depend on vessel and organ involved. The condition is often detected after complications such as myocardial infarction, pulmonary embolism, and stroke. Management includes management of complication and thrombolytic therapy. Thrombosis is a preventable condition and could be avoided by diet and weight control, control of blood pressure, regular exercise, change of occupation, early detection and treatment of certain conditions with anticoagulants or antiplatelet drugs.  

Patient Information

  • Definition: Formation of clot within vessel wall is called thrombosis. Thrombosis cause stagnancy of blood flow within vessels by narrowing the lumen which may precipitate edema if vein is involved or ischemia of tissue if artery is involved. Clot may dislodge from its original position leading to embolism in organ where it is lodged. Symptoms and sign of thrombosis depend on vessel and organ involved.
  • Cause: Thrombosis occurs as a result of like sedentary behavior, prolonged sitting or standing, occlusion of vessels by tumors, atrial or ventricular fibrillation, shock, heart failure, uncontrolled blood pressure, stress, atheroma, infection and altered blood flow and deficiency of certain coagulation proteins.
  • Symptoms: Swelling of leg, discoloration of leg, pain in leg, acute chess pain, breathlessness, cough, hemoptysis, dizziness, confusion, limb weakness, sensory dysfunction, speech disorders, facial asymmetry, bladder dysfunction, abnormal gait, sweating, palpitation, anxiety and syncope may occur.
  • Diagnosis: Objective of workup is confirming obstruction of vessel lumen by imaging studies. ECG, complete blood count (CBC), kidney function test, liver function test, urine examination and blood coagulation profile must be done to rule out complications and set baseline. Depending on complications other investigations may be advised.
  • Treatment: Treatment is directed towards two aspects. Treatment of complication and treatment to dissolve as well prevent recurrence of thrombus. Treatment of complication like swelling and pain of leg in DVT are managed by stockings and NSAIDS. Myocardial ischemia/infarction with centrally acting analgesics, nitroglycerine and life support. Pulmonary thromboembolism with oxygen, and other life support, antibiotics. Whatever is a complication cornerstone of treatment is dissolving blood clot and prevent recurrence. Thrombolytic drugs like streptokinase, human tissue plasminogen activator are used to dissolve clot. For prevention of thrombus formation anticoagulants like heparin, warfarin, and dabigatran are used. Anticoagulant and thrombolytic therapy needs routine INR monitoring [10].

References

  1. Martinelli I, Mannucci PM, De Stefano V, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 1998; 92:2353.
  2. Mateo J, Oliver A, Borrell M, et al. Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism--results of the Spanish Multicentric Study on Thrombophilia (EMET-Study). Thromb Haemost 1997; 77:444.
  3. Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008; 112:19.
  4. Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism--pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001; 86:809.
  5. Seguí R, Estellés A, Mira Y, et al. PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects. Br J Haematol 2000; 111:122.
  6. Browse NL. The painful deep-vein syndrome. Lancet 1970; 1:1251
  7. Koster T, Rosendaal FR, de Ronde H, et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342:1503.
  8. Prandoni P, Bernardi E. Upper extremity deep vein thrombosis. Curr Opin Pulm Med 1999; 5:222.
  9. Christiansen SC, Cannegieter SC, Koster T, et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293:2352.
  10. Sørensen HT, Sværke C, Farkas DK, et al. Superficial and deep venous thrombosis, pulmonary embolism and subsequent risk of cancer. Eur J Cancer 2012; 48:586.
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