BACKGROUND

Multiple venous malformations (VMs) pose some of the difficult challenges in the practice of medicine today. The clinical presentations are extremely wide and range from asymptomatic birthmarks to life-threatening hemorrhages. Because of the rarity of these lesions, experience in their diagnosis and management by clinicians is limited. This augments the enormity of the problem and can lead to misdiagnoses, inadequate treatment, high complication rates, and poor patient outcomes. Venous malformations are dilated venous, capillarovenous, and lymphatic channels with weak walls. Patients with VMs may have raised D-dimer (Table 1). Raised D-dimer level is associated with three types of malformations:^1,2 sporadic venous (unifocal, multifocal) malformation; capillarovenous malformation; Klippel–Trenaunay syndrome. Disseminated intravascular coagulation (DIC) is a well-known cause of raised D-dimer and leads to derangement of coagulation profile and has poor management outcome.³ But the high level of D-dimer seen in localized intravascular coagulopathy (LIC) can lead to misdiagnosis of DIC. Localized intravascular coagulopathy is seen as abnormally high D-dimer in few VMs.⁴ Phleboliths are seen only in cases of sporadic VMs. Venous malformations are slow-flow vascular malformations present at birth, and LIC causes pain and thrombosis within a lesion and severe bleeding during surgical procedures.^5,6 Klippel–Trenaunay syndrome is also a cause of raised D-dimer levels and it is a triad of hemangiomas, varicose vein, and hemihypertrophy of the limb.²

CASE REPORT

A 22-year-old female having multiple congenital VMs at lateral canthus of right eye, left parotid gland, anterolateral aspect of right knee joint, left gluteal region, left knee joint anteriorly, abdominal wall, inferior angle of right scapula, dorsum of left foot, and sole of left foot (Figs 1 to 9) presented with fracture of shaft of left femur on trivial trauma. During her management at the primary care center by attending surgeon, she had excessive bleeding on the incision, so she was referred to our tertiary care center. On examination, the patient was found to be severely anemic. She had VMs as described and these VMs were partially compressible and painful. On deep palpation, phleboliths were felt. At presentation, her hemoglobin was 3.9 gm/dL, platelet count 70,000/mm³, prothrombin time (PT) 21.8 seconds, international normalized ratio 1.77, activated partial thromboplastin time (aPTT) 43.6 seconds, D-dimer 1102.0 ng/mL, serum bilirubin 0.52 mg/dL, C-reactive protein 6 mg/L, plasma fibrinogen 170.0 mg/dL, and serum antinuclear antibodies 5.74 units with normal liver and kidney function tests. The X-ray of left thigh showed displaced fracture femur shaft with multiple 2–5 mm circular, well-defined calcifications suggestive of phleboliths over thigh and pelvic soft tissue region (Fig. 10). Color Doppler study of left lower limb confirmed the presence of slow flow VMs and phleboliths. Color Doppler ultrasonography of left parotid region showed 20 × 27 × 35 mm partially compressible multiloculated hypoechoic cystic intraparenchymal lesion in the superficial compartment of parotid gland suggestive of slow-flow VM. Conformational magnetic resonance imaging for the presence of VMs in internal organs was not done because of the metallic bone traction in situ.

DISCUSSION

Vascular anomalies are divided into two groups: Vascular tumors and vascular malformations. Hemangioma is the most common vascular tumor that usually appears postnatally. It exhibits rapid growth due to cellular proliferation, followed by inevitable involution. Hemangiomas have high-velocity flow in multiple vascular channels. On the contrary, vascular malformations are present since birth and grow proportionally with the growth of patient. They are subdivided according to the affected vessel type into capillary, venous, arterial, and lymphatic malformations. They are slow-flow or fast-flow lesions. When malformations affect more than one vessel type, the combined lesions are named according to the affected vessel, e.g., capillarovenous and capillaro-lymphatico-VM (Flow Chart 1).⁷ Venous malformation can also occur in Klippel–Trenaunay syndrome (capillaro-lymphatico-VM with limb hypertrophy) and Maffucci syndrome (multiple endochondromas associated with multiple hemangioendothelioma and high incidence of malignancy).^8,9 Our patient presented with multiple congenital vascular malformation present at lateral canthus of right eye, left parotid gland, anterolateral aspect of right knee joint, left gluteal region, left knee joint anteriorly, abdominal wall, inferior angle of right scapula, dorsum of left foot, and sole of left foot along with slow-flow VM present in parotid. The screening for the presence of VMs in internal organs could not be done. The presence of phleboliths favors VM, which was evident in soft-tissue X-ray of our patient. Due to blood stagnation, thrombosis can occur, leading to phlebolith formation.^10,11 Multiple VMs are more common in females than males and more on left side of the body. We excluded Klippel–Trenaunay syndrome because there was no evidence of limb hemihypertrophy. D-dimer is the degradation product of cross-linked fibrin; therefore, it reflects ongoing activation of the hemostatic system. Elevated D-dimer levels reflect ongoing activation of the hemostatic and thrombolytic system, providing clinical utility in the diagnosis of DIC, deep vein thrombosis, and evaluation of thrombus formation. Additionally, D-dimer levels may be elevated in the setting of pregnancy, inflammation, malignancy, trauma, postsurgical treatment, and liver disease. It has been seen that higher VM severity scores (as in Table 2)⁷ are associated with more severe LIC and bone fracture.¹² In the view of deranged coagulation profile with raised D-dimer level in the presence of trauma, the patient was initially managed as a case of DIC and her surgery for fracture femur could not be done initially. Color Doppler of lower limb was done to rule out the presence of DVT as a cause of raised D-dimer. She was transfused 16 units of fresh frozen plasma, 18 units of platelets, and 3 units of packed red blood cells, but persistently raised D-dimer level and deranged coagulation profile like thrombocytopenia, raised PT and aPTT without any hemorrhagic manifestation along with presence of multiple phleboliths clinched the diagnosis of LIC. D-dimer is also raised in capillarovenous malformations but they are not associated with phleboliths and hence, were excluded. Low-molecular-weight heparin was started after the diagnosis of LIC and patient was shifted to the orthopedic department for the definitive management of fracture femur after stabilization of patient coagulation profile.

Fig. 1:

Venous malformations around left knee joint

Fig. 2:

Venous malformations above right knee joint

Fig. 3:

Venous malformations at left buttock

Fig. 4:

Venous malformations near left ankle

Fig. 5:

Venous malformations on sole of left foot

Fig. 6:

Venous malformations–outer canthus of right eye

Fig. 7:

Venous malformations over abdomen

Fig. 8:

Venous malformations near inferior angle of right scapula

Fig. 9:

Venous malformations–left parotid gland

Fig. 10:

Multiple phleboliths: X-ray left femur anteroposterior view

Flow Chart 1:

Classification system of the International Society for the Study of Vascular Anomalies (1996).⁷ AVM: Arteriovenous malformation; CM: Capillary malformation; LM: Lymphatic malformation

CONCLUSION

Venous malformations are associated with spontaneous thrombosis and thrombolysis. This is witnessed by the presence of phleboliths and elevated D-dimer levels (>0.5 μg/mL). This phenomenon is named LIC.² D-dimer levels are often very high >1.0 μg/mL in 25% cases even if these otherwise healthy patients do not have underlying conditions that increase D-dimer levels. An LIC is usually well-tolerated during everyday life. However, a few patients are at risk of potential aggravation of LIC to DIC with dramatic bleeding during a surgical excision, and marked consumption of platelets, coagulation factors, and fibrinogen.⁴ Therefore, measurement of D-dimer levels is mandatory in the management of VMs.¹³ Venous malformation is not the only disease that can increase D-dimer levels highly and persistently in otherwise healthy patients, other conditions like glomerulonephritis, chronic rejection of renal allograft, and normal pregnancy may also lead to chronic LIC.¹⁴ Elevated D-dimer levels in vascular anomalies suggest a venous component in 96.5% of patients. This can help differentiate glomuvenous malformations from other multifocal venous lesions. It can also detect a venous component in combined and syndromic malformations. Low-molecular-weight heparin is used to relieve pain caused by LIC and to prevent decompensation of severe LIC to DIC.⁴

CLINICAL SIGNIFICANCE