Unusual Deep Vein Thromboses

Dr. Karl von Kemp Centrum voor Hart- en Vaatziekten UZ Brussel Unusual Deep Vein Thromboses

 Upper extremity deep vein thrombosis • Spontaneous • Catheter-associated  Cerebral venous thrombosis  Retinal vein thrombosis

2 Unusual DVT BSIM 3.12.2010 Part 1 : Upper extremity venous thrombosis

Spontaneous upper extremity venous thrombosis Catheter-induced upper extremity venous thrombosis Spontaneous upper extremity venous thrombosis

 “Paget-Schroetter syndrome”  “Effort thrombosis”

 Etiology : • Extrinsic compression at the thoracic outlet • Hypercoagulability : minor role

4 Unusual DVT BSIM 3.12.2010 Anatomical Factors Predisposing to Paget–Schroetter Syndrome.

5 Unusual DVT BSIM 3.12.2010 Spontaneous upper extremity venous thrombosis

 “Paget-Schroetter syndrome”  “Effort thrombosis”  Etiology : • Extrinsic compression at the thoracic outlet • Hypercoagulability : minor role  Clinical presentation: • Dull aching pain axilla/shoulder • Swelling of arm or hand, cyanosis, dilated collaterals • Symptoms increase with exercise, improve with rest and elevation of the arm • Preceding strenuous exercise

6 Unusual DVT BSIM 3.12.2010 Paget–Schroetter Syndrome

7 Unusual DVT BSIM 3.12.2010 Spontaneous upper extremity venous thrombosis

DIAGNOSIS  Only 50 % of clinically suspected UEVT have a positive phlebogram.  Digital substraction phlebography  Duplex doppler ultrasound • Sensitivity 70 – 100 %, specificity 93 % • Proximal subclavian vein shadowed by clavicle and sternum • Useful for screening purposes  MRI : sensitivity for non-occlusive thrombi ??  CT : insufficient data

8 Unusual DVT BSIM 3.12.2010 Right Subclavian Angiogram Revealing Chronic Nonocclusive Thrombus (Thick Arrow) and Irregularities and Aneurysmal Dilatation (Thin Arrow) in the Subclavian Vein.

9 Unusual DVT BSIM 3.12.2010 Spontaneous upper extremity venous thrombosis

EVOLUTION  Pulmonary embolism in > 30 %  Conservative management (anticoagulation only) : < 50 % are asymptomatic after 5 years  Thrombolysis : > 75 % are asymptomatic after 5 years  An invasive approach is favored • Younger and physically active patients • Potential for severe physical limitation by chronic venous insufficiency

10 Unusual DVT BSIM 3.12.2010 Spontaneous upper extremity venous thrombosis

 MANAGEMENT  No firm data  Patients with recanalisation of the subclavian vein fare better.  Many patients do well even with persistent venous occlusion.  A combined approach probably gives the best long term outcome but is not necessary for all patients.

11 Unusual DVT BSIM 3.12.2010 Suggested management for Paget-Schroetter syndrome (1/3)

Arm venogram Positive Negative Catheter-directed Investigate other thrombolysis causes for symptoms

Succesful lysis No lysis

Anticoagulation Anticoagulation 6 to 8 weeks 3 months

Repeat venogram No abnormality

Venous compression Discontinue anticoagulation

Surgical correction Evaluate for thrombophilia

12 Unusual DVT BSIM 3.12.2010 Suggested management for Paget-Schroetter syndrome (2/3)

Surgical correction

Anticoagulation 6 to 8 weeks

Repeat venogram No abnormality

Venous stenosis Discontinue anticoagulation

Balloon angioplasty Evaluate for thrombophilia

Anticoagulation 6 to 8 weeks

Repeat venogram

13 Unusual DVT BSIM 3.12.2010 Suggested management for Paget-Schroetter syndrome (3/3)

Repeat venogram after balloon angioplasty

Persistent stenosis Collaterals absent

Collaterals present Discontinue anticoagulation

Evaluate for thrombophilia Consider indefinite anticoagulation or repeat angioplasty

14 Unusual DVT BSIM 3.12.2010 Evaluation for thrombophilia

Recommendation of the Thrombosis Guidelines Group :  A standard thrombophilia screening is recommended for a first unexplained DVT at age < 45, in case of family history of DVT, or in DVT at an unusual location.  Determine antithrombin, protein C, protein S, APCR, prothrombin G20210A mutation, anticardiolipin antibodies, lupus anticoagulant, factor VIII and homocystein.  See www.bsth.be for details (TGG recommendations)

15 Unusual DVT BSIM 3.12.2010 When to screen for thrombophilia ?

 At diagnosis and before initiation of therapy.

 Activation of the coagulation cascade can cause false- positive and false-negative results.

 The most reliable time is 1 month after stopping the anticoagulant treatment.

16 Unusual DVT BSIM 3.12.2010 Catheter-induced upper extremity venous thrombosis (UEVT).

 Superficial thrombosis due to peripheral catheters.  Endothelial trauma and vessel wall inflammation.  Risks : • Embolism • Post-thrombotic symptoms

17 Unusual DVT BSIM 3.12.2010 Risk factors for catheter-induced UEVT.

 PICC = central catheter  Tip in v. brachiocefalica.  Infection  Hormonal therapy (if + thrombophilia; or IVF)  Chemical irritation (chemotherapy)  Highest incidence in cancer patients • Up to 60 % • 75 % are asymptomatic

18 Unusual DVT BSIM 3.12.2010 Clinical presentation of catheter-induced UEVT.

 Very often asymptomatic  Inability to draw blood from catheter  Congestion of venous collaterals  Pain/tenderness at insertion site, induration, erythema : ΔΔ local tumor invasion.  Oedema, increases with exercise.  Pulmonary embolism may be the first symptom  High index of suspicion requested !

19 Unusual DVT BSIM 3.12.2010 Diagnosis of catheter-induced UEVT.

 Duplex ultrasound • Limitations cfr. Paget-Schroetter syndrome • Prior to repeat catheterisation  Venography • Through the catheter • Conventional venography : on strict indication.

20 Unusual DVT BSIM 3.12.2010 Management of catheter-induced UEVT (1).

 More conservative than P.S. syndrome • Older pts, more sedentary, live shorter • Have more severe problems than venous insufficiency  Prevention of embolisation : treatment = treatment for lower extremity DVT.  Maintain catheter function !  Removal of the catheter ? (does not eliminate the need for anticoagulation).  What in asymptomatic UEVT ?

21 Unusual DVT BSIM 3.12.2010 Management of catheter-induced UEVT (2).

 Thrombolysis : not recommended  Instillation of a fibrinolytic agent in an occluded catheter can be considered (rTPA or urokinase)  Prophylactic anticoagulation (LMWH) may reduce thrombosis, does not reduce occlusive thrombi : not recommended

22 Unusual DVT BSIM 3.12.2010 Pacemaker leads and UEVT

 Frequent : 5 – 25 % by venography  Only 1 – 3 % have symptomatic UEVT  ICD = pacemaker  Main problem : replacing electrodes or upgrading the device (CRT)  Duplex ultrasound should always precede such a procedure.  Anticoagulation (for cardiac indication) seems to protect from UEVT.

23 Unusual DVT BSIM 3.12.2010 Pacemaker leads and UEVT

Predictors of UEVT :  Multiple leads vs single lead  Hormone therapy  History of DVT  Insertion of a temporary PM preceding the definitive PM  Presence of a PM preceding insertion of an ICD  Dual coil leads

24 Unusual DVT BSIM 3.12.2010 Management of PM-lead-associated UEVT

 Asymptomatic pts are usually not treated.  Anticoagulation is the cornerstone of therapy in symptomatic patients.  Thrombolysis improves early patency but does not reduce late post-thrombotic syndrome.  Removal of a non-functional lead before inserting a new lead.

25 Unusual DVT BSIM 3.12.2010 Part 2 : Cerebral venous thrombosis Cerebral Venous Thrombosis

 Less common type of stroke  Increased awareness and increased availability of MRI leads to increased diagnosis.  International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) (Stroke 2009)  Younger patients (mean : 39 y).  Female predominance (pregnancy – puerperium – contraception)

27 Unusual DVT BSIM 3.12.2010 Cerebral Venous Thrombosis : Pathogenesis

Obstruction of dural sinus

Increased venous pressure

↑ Venular and Impairment of CSF Capillary pressure absorption

↓ Capillary Venous and Blood-brain Increased perfusion capillary rupture barrier disruption Intracranial pressure

↓ Cerebral Parenchymal Vasogenic perfusion haemorrhage edema

↓ Cerebral blood flow

Failure of energetic Cytotoxic metabolism edema

28 Unusual DVT BSIM 3.12.2010 Cerebral Venous Thrombosis : Clinical Aspects

Highly variable clinical presentation :  Intracranial hypertension syndrome : headache ± vomiting (89 %), papilledema, visual problems  Focal syndrome : focal deficits, seizures.  Encephalopathy : multifocal signs, mental status changes, stupor, coma

29 Unusual DVT BSIM 3.12.2010 Frequency of Thrombosis of the Major Cerebral Veins and Sinuses.

30 Unusual DVT BSIM 3.12.2010 Postmortem Views of Sinus Thrombosis.

31 Unusual DVT BSIM 3.12.2010 MRI of Sinus Thrombosis.

Stam J. N Engl J Med 2005;352:1791-1798.

32 Unusual DVT BSIM 3.12.2010 Angiographic Image (Venous Phase) of Sinus Thrombosis.

33 Unusual DVT BSIM 3.12.2010 CT Imaging of Sinus Thrombosis.

Stam J. N Engl J Med 2005;352:1791-1798.

34 Unusual DVT BSIM 3.12.2010 Causes of and Risk Factors Associated with Cerebral Venous Sinus Thrombosis

 Genetic prothrombotic conditions  Inflammatory bowel disease  Antithrombin deficiency  Behçet’s syndrome  Protein C and protein S deficiency  Hematologic conditions  Factor V Leiden mutation  Polycythemia, primary and secondary  Prothrombin G20210A mutation  Thrombocythemia  Hyperhomocysteinemia caused by gene  Leukemia mutation in MTHF reductase  Anemia, including paroxysmal nocturnal  Acquired prothrombotic states hemoglobinuria  Nephrotic syndrome  Drugs  Antiphospholipid antibodies  Oral contraceptives  Homocysteinemia  Asparaginase  Pregnancy  Mechanical causes, trauma  Puerperium  Head injury  Infections  Injury to sinuses or jugular vein, jugular  Otitis, mastoiditis, sinusitis catheterisation  Meningitis  Neurosurgical procedures  Systemic infectious disease  Lumbar puncture  Inflammatory disease  Miscellaneous  SLE  Dehydration, especially in children  Wegener’s granulomatosis  Cancer  Sarcoidosis  Stam, J. N Engl J Med 2005; 352 ; 1791

35 Unusual DVT BSIM 3.12.2010 Detection of thrombophilia in CVT.

• A cause of CVT will be found in 65 to 85 % of patients.

• There is generally an association of a genetic thrombophilia with a precipitating factor : oral contraception, pregnancy of puerperium, cranial trauma, lumbar puncture.

• In patients over 40 without identified etiology, search for malignancy.

36 Unusual DVT BSIM 3.12.2010 Prognosis of CVT

 5 % die in the acute phase  15 % overall death or dependency  Low risk of recurrence  Predictors of poor long-term prognosis : • Central nervous system infection • Malignancy • Thrombosis of the deep cerebral veins • Hemorrhage on CT or MRI • Glasgow coma scale < 9 on admission • Mental state abnormality • Age > 37 years • Male gender.

37 Unusual DVT BSIM 3.12.2010 Treatment of CVT (1)

 Anticoagulation (LMWH followed by vit K antagonists) is recommended.  Anticoagulation appears safe even in the presence of intracerebral or subarachnoid hemorrhage.  Endovascular thrombolysis could be performed at experienced centers in patients with poor prognosis who worsen despite adequate anticoagulation.

38 Unusual DVT BSIM 3.12.2010 Treatment for CVT (2)

 Anticoagulant treatment will be administered for 6 to 12 months.  Chronic anticoagulation is recommended for patients with prothrombotic conditions, including the antiphospholipid syndrome.  Oral contraception should be stopped.  CVT is not a contra-indication for subsequent pregnancy.

39 Unusual DVT BSIM 3.12.2010 Part 3 : Retinal vein thrombosis Retinal vein occlusion

 is a frequent cause of loss of vision in the elderly;  is the second most frequent vascular disease of the retina (after diabetes retinopathy).  Stasis and thrombosis in the retinal vein are caused by atherosclerotic or inflammatory damage in the adjacent artery.  Loss of vision is mainly due to macular edema (and neovascularisation, vitreous hemorrhage, retinal detachment or neovascular glaucoma).

41 Unusual DVT BSIM 3.12.2010 Retinal vein occlusion

 Is weakly associated with all thrombophilic states.  Arterial hypertension is the strongest risk factor.  There is a weaker association with diabetes, hyperlipidemia, smoking and renal disease.

42 Unusual DVT BSIM 3.12.2010 Types of retinal vein occlusion

 Branch retinal vein occlusion (at an AV intersection)  Central retinal vein occlusion (at lamina cribrosa sclerae)  Branch RVO is 4 x more common than central RVO and has a better prognosis.

 Perfused or non perfused RVO

43 Unusual DVT BSIM 3.12.2010 Branch Retinal-Vein Occlusion in the Superotemporal Quadrant of the Right Eye

44 Unusual DVT BSIM 3.12.2010 Nonperfused Central Retinal-Vein Occlusion in the Left Eye

45 Unusual DVT BSIM 3.12.2010 Diagnostic workup of RVO

 Ophtalmologic assessment : fundoscopy, fluorescein angiography, OCT…  Systemic workup :  1 : Check for cardiovascular risk factors • No evidence that treatment of AHT or other risk factor influences visual prognosis • RVO should be considered end-organ damage by AHT, implying more aggressive management.

46 Unusual DVT BSIM 3.12.2010 Systemic workup of RVO

 2. Check for cardiovascular disease (stroke, PAD, coronary artery disease).  3. Routine laboratory testing : glycemia, HbA1c, renal function, lipid levels, CBC (hyperviscosity syndrome ?).  4. Thrombophilia testing  In younger patients (< 50)  Notion of preceding thrombotic disorders  Bilateral RVO

47 Unusual DVT BSIM 3.12.2010 Treatment of renal vein occlusion.

 No indication for anticoagulation.  Local treatment  Laser therapy  Intravitreal steroids  Intravitreal anti VEGF drugs

48 Unusual DVT BSIM 3.12.2010 Conclusion.

 The same basic process (venous thrombosis) can cause damage by a variety of mechanisms, depending on the site involved.  Treatment for the same basic process can vary from very aggresive to strict abstinence of interfering with the thrombotic process.

49 Unusual DVT BSIM 3.12.2010 Assessment of Cardiovascular Risk in Patients with Retinal-Vein Occlusion

50 Unusual DVT BSIM 3.12.2010 51 Unusual DVT BSIM 3.12.2010 52 Unusual DVT BSIM 3.12.2010 53 Unusual DVT BSIM 3.12.2010