Venous thrombosis deep in the upper extremity I80.28

Sudden or gradual, partial or complete occlusion of at least one segment of the deep leading and muscle veins of upper limb veins and thoracic aperture caused by a thrombus with a tendency to grow and the risk of embolization into the lungs. These include jugular, brachiocephalic, subclavian and axillary veins, as well as the more distal brachial, ulnar and radial veins.

Deep vein thrombosis of the upper extremity (TV-OE) is classified:

• Primary deep vein thrombosis of the upper extremity (idiopathic, anatomical variations)
• Secondary deep vein thrombosis of the upper extremity (associated with tumor diseases, intravenous catheters, pacemakers)

Risk of DVT is 1:1,000 per year; TV-OE affect about 4-10% of the total population (Encke A et al. 2016) with increasing incidence. At 80%, secondary DVT OUs are much more common than primary DVT OUs (Sajid MS et al. 2007).

Slowing of blood flow, endothelial injuries (see below endothelium) in central venous catheters and pacemakers. Further risk factors are tumor diseases, age >40 years, immobilization, overexertion (thrombosis par èffort), thromboembolic events in the history.

In particular, the combination of irritation of the vessel wall by a central venous valve or by chemotherapeutic agents and a tumour-related hypercoagulopathy of the blood seems to favour the formation of a DVT-OE. In >50% of patients with a DVT-OE, a central venous valve or pacemaker is located in the affected area (Spencer FA et al. 2007). In up to 49% of patients with DVT-OE a tumour is present (Heil J et al.2018). An underlying malignant disease increases the risk by a factor of 18 compared to non-tumour patients. Surgical interventions represent a further risk.

Occurrence especially in middle and higher age (median 60 years).

Most frequently affected are the subclavian (62%), axillary (45%) and jugular (45%) veins, although >1 thrombosis can also be detected.

Signs of venous congestion such as swelling, pain, edema, cyanosis, dilatation of the superficial veins. 33-60% of DVT-OE are asymptomatic (Sajid MS 2007). The risk of pulmonary embolism is highest during the first 3 days of thrombosis development.

Indication of thrombosis in the area of the subclavian/axillary vein may be localised neck or shoulder pain. Weakness or paraesthesia in the affected arm as well as elevated body temperatures may also be indications of DVT-OE.

Diagnostic algorithm based on the Constans criteria:

• CVC or pacemaker (1 point)
• Localized pain (1 point)
• Unilateral swelling (1 point)
• Alternative diagnosis likely to cause symptoms (1 point less)

Assessment: =/>2 points: TVT-OE probable); determination of the D-dimers (>500 ug/L)

Furthermore:

• Duplex compression sonography (method of first choice) taking into account the clinical probability.
• In case of uncertain or negative findings in compression sonography: phlebography or D-dimer test.
• Diagnosis of thrombophilia: Exact family history. Determination of laboratory parameters in individual cases: resistance to activated protein C (factor V Leiden mutation), deficiency of protein C, protein S, antithrombin III, presence of a lupus anticoagulant or anti-cardiolipin antibody, disturbances in fibrinolysis or hyperhomocysteinemia, possible clarification of family members who may also have a tendency to thrombosis.

The therapy is based on the treatment of deep vein thrombosis of the lower extremity.

Initial anticoagulation:

Full heparinization in therapeutic dosage (good evidence): Weight-adapted with low molecular weight heparin (NMH) e.g. nadroparin (fraxiparin) 2 times/day 0.1 ml/10 kg KG s.c.; only in exceptional cases with unfractionated heparin. S.u. Heparin, systemic.

For the initial therapy of DVT-UE (deep vein thrombosis of the lower extremity), direct oral anticoagulants (DOAC) such as rivaroxaban (initial 2x15mg p.o./day, after 3 weeks 1x20mg p.o./day) and apixaban (initial 2x10mg p.o./day, after 7 days maintenance dose 2x5mg p.o./day). They can also be used in the TVT-OE in this dosage.

For maintenance therapy, vitamin K antagonists have so far been used extensively. The target range of the International Normalized Ratio (INR) is 2.0-3.0. However, DOACs, whose advantage is the reduction of major bleeding, are increasingly used in maintenance therapy. Furthermore in the renunciation of INR controls.

The duration of maintenance therapy is 3-6 months, depending on the cause.

Alternative: Regional hyperthermic fibrinolytic perfusion: New method derived from hyperthermic limb perfusion in malignant melanoma. Advantages: No AI, no age limits, no systemic NW.

Thrombolysis: Only in exceptional cases possibly indicated in young people with extensive initial thrombosis, short medical history, thrombi washed around, acute threat to the extremity and exclusion of thrombophilia. Contraindications must be observed extremely strictly! Treatment by thrombolysis or thrombectomy should be reserved for specialised centres with sufficient experience. Preparations: Streptokinase, Urokinase, Alteplase (rtPA, recombinant tissue-type plasminogen activator), Tenecteplase (TNK-t-PA).

Thrombolysis methods: systemic lysis therapy (very high rate of side effects), locoregional lysis therapy.

1. Avila ML et al (2016) Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool. Thromb Res 144:184-191.
2. Encke A et al. (2016) The prophylaxis of venous thromboembolism. Dtsch Ärztebl. Int 113: 532-538
3. EINSTEIN Investigators (2011) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363: 2499-2510
4. Heil J et al (2017) Deep vein thrombosis of the upper extremity. Dtsch Ärztebl 114: 244-249
5. Lewis BE et al (2007) Direct thrombin inhibition during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia. Expert Rev Cardiovasc Ther 5: 57-68
6. Qi X et al (2016) Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients. Med Sci Monit 22:2528-2550.
7. Ridker PM et al (2003) Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 348: 1425-1434
8. Sajid MS et al (2007) Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol.118:10-18.
9. Scurr JH et al (2001) Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial. Lancet. 357: 1485-1489
10. Spencer FA et al (2007) Upper extremity deep vein thrombosis: a community-based perspective.On J med 120:678-684.
11. Turpie AG et al (2002) Venous thromboembolism: pathophysiology, clinical features, and prevention. BMJ 325: 887-890