Thrombosis

Thrombosis: Excerpt from The 5-Minute Pediatric Consult

Char Witmer, MDLeslie Raffini (4th Edition)

Thrombosis - BASICS

Thrombosis - description

Pathologic arterial or venous intravascular occlusion by thrombus, which interferes with normal blood flow.

The following are common thrombotic events:

• Deep venous thrombosis: Involves large systemic veins outside CNS
• Cerebral sinovenous thrombosis: Involves intracranial venous sinuses
• Ischemic stroke: CNS arterial occlusion with infarction of brain tissue
• Intracardiac thrombosis: Mural, valvular, or foreign body associated
• Femoral artery thrombosis: Associated with vessel catheterization
• Renal vein thrombosis: In the neonatal period; may be unilateral or bilateral
• Myocardial infarction: Kawasaki disease or with severe familial hypercholesterolemia
• Budd–Chiari syndrome: Thrombosis of the hepatic vein
• Portal vein thrombosis

Thrombosis - epidemiology

• Incidence of venous thrombosis in children is estimated at 0.7 per 100,000 per year. It is likely that the actual incidence is higher.
• Idiopathic thrombosis is rare in children.
• 2/3 of children with a thrombotic event have a predisposing underlying condition.
• Central venous lines are the most common risk factor for venous thrombosis in children.

Thrombosis - risk factors

• Neonatal:
  • Prematurity
  • Maternal diabetes
  • Umbilical catheters or other central lines
  • Sepsis
  • Polycythemia
  • Perinatal asphyxia
• Malignancy/Bone marrow disorders:
  • Leukemia (hyperleukocytosis, acute promyelocytic leukemia)
  • Myeloproliferative disorders
  • Paroxysmal nocturnal hemoglobinuria
• Medications:
  • L-Asparaginase
  • Oral contraceptives
  • Heparin (heparin-induced thrombocytopenia)
  • Steroids
• Anatomic:
  • Indwelling catheters
  • Congenital heart disease
  • Prosthetic heart valves
  • Intracardiac baffles
  • Tumor compression
  • Atresia of the inferior vena cava
  • Thoracic outlet obstruction (Paget–Schroetter syndrome)
  • May–Thurner syndrome (compression of the left iliac vein by the artery crossing over it)
• Miscellaneous:
  • Infection
  • Trauma
  • Surgery
  • Obesity
  • Prolonged immobilization or paralysis
  • Dehydration
  • Antiphospholipid syndrome
• Risk factors/conditions specific for arterial disease:
  • Kawasaki disease
  • Takayasu arteritis
  • Hyperlipidemia
  • Antiphospholipid syndrome

Thrombosis - associated conditions

• Nephrotic syndrome
• Inflammatory disorders
• Liver disease
• Sickle cell disease
• Diabetes mellitus

Thrombosis - DIAGNOSIS

• Phase 1: Perform complete history and examination; establish diagnosis using the appropriate radiographic study.
• Phase 2: Send initial laboratory studies (CBC, PT/aPTT, D-dimer, antithrombin) and begin anticoagulation therapy with unfractionated heparin or low-molecular-weight heparin.
• Patients with life- or limb-threatening thrombosis may require thrombolysis.
• Phase 3: Complete lab workup for hypercoagulable state; outpatient anticoagulation; follow thrombosis radiologically

Thrombosis - signs & symptoms

Thrombosis - history

• Current (or recent) central venous or arterial catheter: Most significant risk factor for thrombosis
• Presence of risk factors previously listed
• Family history of thrombosis: May be an inherited thrombophilia
• Personal history of thrombosis: Patients with history of thrombosis are at increased risk of recurrence.
• Neonatal seizure: Common and often the only presenting sign for cerebral sinovenous thrombosis or arterial ischemic stroke
• Chest pain or shortness of breath: Suggestive of pulmonary embolism

Thrombosis - physical exam

• Unilateral swelling/edema of a limb: Extremity deep venous thrombosis
• Bilateral lower extremity edema of a limb: Thrombosis of the inferior vena cava
• Plethoric, swollen head and neck: Superior vena cava syndrome
• Pale extremity with decreased perfusion/pulses: Arterial thrombosis
• Abdominal mass and/or mass in neonate: Renal vein thrombosis
• Tachypnea, shallow respirations: Pulmonary embolism
• Unexplained hepatosplenomegaly: Hepatic or portal vein thrombosis
• Superficial dilated cutaneous veins distal to the site of venous occlusion: Postphlebitic syndrome
• Chronic discoloration (darkening) of the skin, ulcerations, pain, intermittent swelling: Postphlebitic syndrome

Thrombosis - tests

Thrombosis - lab

• General evaluation of the hemostatic system:
  • PT, aPTT, fibrinogen
  • CBC with platelet count
  • D-dimer
• The following tests are used to investigate for a prothrombotic state:
  • Phase 1:
    • Factor V Leiden mutation analysis
    • Prothrombin 20210A mutation analysis
    • Lupus anticoagulant screen (dilute Russell viper venom time, aPTT)
    • Anticardiolipin antibodies (IgG, IgM)
    • Anti-β2 glycoprotein antibodies (IgG, IgM)
    • Protein C activity
    • Protein S activity
    • Antithrombin activity
    • Fasting homocysteine
    • Fasting lipoprotein(a)
  • Phase 2: For patients whose phase 1 studies are normal, but there is a strong family history of thrombosis:
    • Factor VIII activity
    • Plasminogen
    • Thrombin time or dysfibrinogenemia screen
    • Activated protein C resistance clotting assay
    • Heparin cofactor II
    • Plasminogen activator inhibitor type 1

Thrombosis - imaging

Radiologists should be consulted for choosing the best imaging study for diagnosis and follow-up.

• Contrast angiography: Gold standard, but invasive and sometimes technically difficult to perform in small children
• Ultrasound: Most commonly used imaging study because of noninvasiveness, absence of radiation, and ability to be performed at the bedside
• In the diagnosis of upper extremity–related deep venous thrombosis, often a combination of ultrasound and venography is necessary:
  • Compression ultrasound of the upper central veins may be impeded by the distal end of the clavicle.
  • Venography has poor sensitivity for diagnosing thrombosis of the internal jugular veins.
  • Recommended approach for diagnosis of an upper extremity thrombosis is to start with ultrasound and proceed to venography if the ultrasound is normal and there is a high clinical suspicion.
• Electrocardiogram may be useful in evaluating atrial thrombi, which may result from central venous catheters.
• Pulmonary angiography, ventilation–perfusion scans, spiral CT scans are the imaging studies used for the diagnosis of pulmonary embolism, although none of these have been studied in children.
• In patients with a pulmonary embolism, it is important to look for a source of thrombosis in the upper and lower extremities.
• Other diagnostic imaging options include CT or MRV:
  • Noninvasive
  • Sensitivity and specificity not known
  • May be helpful in evaluating proximal thrombosis
• For diagnosis of cerebral sinovenous thrombosis, the most sensitive imaging study is brain MRI with venography.

Thrombosis - differencial diagnosis

Primary prothrombotic states:

• Inherited:
  • Factor V Leiden gene mutation
  • Prothrombin 20210A gene mutation
  • Protein C deficiency
  • Protein S deficiency
  • Antithrombin deficiency
  • Homocystinemia (mild to moderate) from minor defects in enzymes such as methylenetetrahydrofolate reductase or severe, in homocystinuria
  • Elevated lipoprotein(a)
  • Plasminogen deficiency
  • Dysfibrinogenemia
  • Heparin cofactor II deficiency
• Acquired: Antiphospholipid antibody syndrome

• Normal ranges for coagulation tests are age dependent: Diagnosing an inherited deficiency in any of the anticoagulant proteins can be difficult in the neonatal period. Repeat testing at 6–12 months of age is necessary.
• Consumption can occur during acute thrombosis; therefore, low levels of the anticoagulant proteins must be repeated.
• Warfarin will decrease the levels of protein C, protein S, and clotting factors II, VII, IX, and X.

Thrombosis - TREATMENT

Thrombosis - general measures

• Therapy for acute thrombosis and long-term management is individualized.
• Consult a pediatric hematologist or someone with expertise in pediatric anticoagulant therapy.

Thrombosis - medication

• Unfractionated heparin:
  • Given as a bolus followed by an infusion, adjusted to maintain the aPTT at 1.5–2.5 times baseline
  • Younger children require higher doses of heparin to achieve a therapeutic level.
• Low-molecular-weight heparin:
  • More predictable dose response
  • Given SC twice a day
  • Equivalent in efficacy to unfractionated heparin in the acute management of uncomplicated deep venous thrombosis
  • Renal clearance
• Thrombolytics:
  • Urokinase or recombinant tissue plasminogen activator
  • May be given systemically or locally
  • High risk of bleeding
• Warfarin:
  • Oral anticoagulant
  • Initially started when a patient is already receiving a form of heparin. The heparin is discontinued when the warfarin is in the therapeutic range.
  • Warfarin is adjusted to maintain an international normalized ratio (INR) of 2.0–3.0 for treatment of deep venous thrombosis
  • Used for outpatient management
• Aspirin:
  • Beneficial in stroke and other arterial events
  • Irreversibly inhibits platelet function

Thrombosis - FOLLOW UP

Thrombosis - complications

• Vary depending on the location and severity of the thrombosis
• In deep venous thrombosis, pulmonary embolism is the most significant acute complication. Recurrent thrombosis and postphlebitic syndrome are common chronic complications.
• In arterial thromboembolic disease, the ischemic injury to the involved organ determines the acute and long-term complications.

• Central venous catheter–related thrombosis may be subtle despite extensive damage to the venous system. Recurrent line infection, line occlusion, and prominent venous collaterals on the chest suggest upper extremity deep venous thrombosis. The long-term consequences of this are not known.
• Warfarin can cause purpura fulminans if started in an unheparinized patient.

Thrombosis - bibliography

Andrew M, Monagle PT, Brooker L. Thromboembolic Complications During Infancy and Childhood. Hamilton, Ontario: BC Decker; 2000.
1. Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I22–I30.
2. Line BR. Pathophysiology and diagnosis of deep venous thrombosis. Semin Nucl Med. 2001;31:90–101.
3. Monagle P, Chan A, Chalmers E, et al. Antithrombotic therapy in children. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004;126:645s–687s.
4. van Ommen CH, Peters M. Venous thromboembolic disease in childhood. Semin Thromb Hemost. 2003;29:391–404.

Thrombosis - CODES

Thrombosis - icd9

• 671.9 Unspecified venous complication
• 453.40 Deep vein thrombosis (NOS)

Thrombosis - FAQ

• Q: If an inherited prothrombotic condition is identified, should family members be tested?
• A: Yes, if they have other risk factors for thrombosis such as malignancy, major surgery, oral contraceptives, or obesity.
• Q: When is it appropriate to use low-molecular-weight heparin rather than unfractionated heparin?
• A: There are several potential advantages to low-molecular-weight heparin. The pharmacokinetics are much more predictable, and frequent monitoring is not necessary. It is administered subcutaneously, not intravenously. The risk of bleeding may be slightly lower.Low-molecular-weight heparin cannot be completely reversed with protamine and it is renally cleared.
• Q: When is it appropriate to use thrombolytic therapy?
• A: Studies do not clearly demonstrate a role for thrombolytic therapy in deep venous thrombosis. However, if a thrombus extends on heparin therapy, a pulmonary embolus is suspected, or if the disturbance in blood flow causes ischemia, thrombolytic therapy can be used. Intracranial bleeding is a contraindication. For arterial thrombotic events, thrombolytic therapy is often the treatment of choice because of the rapid resolution of the clot and restoration of blood flow.
• Q: What precautions should be taken for invasive procedures and for athletics when a patient is on anticoagulant therapy?
• A: Lumbar punctures, arterial punctures, and surgical procedures should be avoided. If they are necessary, then the child should have the anticoagulant reversed before the procedure. The child should not participate in contact sports such as football, karate, and boxing. For baseball, a helmet should be worn at all times.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Heart attack

• Back to disease: Heart attack: Introduction
• Next Book Extract About Heart attack: Surveys relating to Heart attack
• More Book Extracts: All Online Books for Heart attack

More Medical Textbooks Online about Heart attack

Review other book chapters online related to Heart attack:

Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

 » Next page: Surveys relating to Heart attack

Rate This Website

What do you think about the features of this website? Take our user survey and have your say:

Website User Survey

Medical Tools & Articles:

Next articles:

• Surveys relating to Heart attack
• Ask Question about Heart attack

Tools & Services:

• Bookmark this page
• Symptom Search
• Symptom Checker
• Medical Dictionary
• Give your feedback

Medical Articles:

• Disease & Treatments Search
• Misdiagnosis Center
• Full list of interesting articles

Forums & Message Boards

• Ask or answer a question at the Boards:
• I cannot get a diagnosis. Please help.
• Tell us your medical story.
• Share your misdiagnosis story.
• What is the best treatment for my condition?
• See all the Boards.

Enter your search terms Submit search form
Search The Web Search wrongdiagnosis.com

Common Health Mistakes

Symptom
Checker

Search Specialists by State and City