Disseminated intravascular coagulation (DIC) is a systemic disorder characterized by hypercoagulability leading to micro and macrovascular clotting and hypoperfusion, resulting in multi-organ dysfunction. Normally, when vascular injury occurs, haemostasis ensures clot formation occur rapidly to prevent excessive blood loss. Resolution of clot is necessary to allow blood flow to resume, such that tissue repair can occur. This process is carefully orchestrated in stages which begins with formation of platelet plug, followed by activation of coagulation cascade which ends with a clot formation. When the clot is firmly formed, coagulation cascade ends and fibrinolysis ensues to dissolve the clot by fibrinolysis. In DIC, the process of coagulation and fibrinolysis become abnormally, often massively, activated leading to systemic coagulation and fibrinolysis.

Disseminated massive activation of the coagulation cascade leads to production of thrombi (which compose mainly of fibrin and platelets) hence depletion of platelet count. Extensive thrombi formation leads to consumption of clotting factors, platelets and anticoagulation factors (protein S, protein C and antithrombin). This consumptive coagulopathy depletes clotting factors and platelets which can then result in massive bleeding.

Causes of DIC include sepsis, malignancy, liver disease, trauma, transfusion reaction due to ABO mismatch, obstetric complications (e.g., preeclampsia, HELLP syndrome, placental abruption), and VTE [1,2]. DIC starts with exposure to a procoagulant like cancer cells or bacteria products such as lipopolysaccharides or tissue factors [3], trauma where damage to endothelium causes release of procoagulant enzymes/ phospholipids.  In cases of DIC where thrombosis is more prevalent, the patients may present with arterial or venous thromboembolism [4].

In Madam RA’s case, she was diagnosed with bilateral lower limb DVT which may have occurred as a combination of reduced mobility as well as DIC triggered by sepsis secondary to bilateral pyelonephritis. DIC is common in bacteria sepsis, with increasing likelihood related to severity of systemic infection [5]. This patient had evidence of bilateral pyelonephritis on CT scan with elevated CRP but blood culture was negative. In terms of pyelonephritis, she seemed to be responding to IV pip-tazocin and gentamicin with a lack of fever.

DIC resulted in massive consumption of coagulation factors and platelets which outpaced their production, as shown by abnormally prolonged clotting times, low fibrinogen levels and thrombocytopenia. Fibrinolysis occur resulting in generation of Fibrinogen Degradation Products (FDP) which inhibit subsequent platelet aggregation and disrupts fibrinogen polymerization as part of clot formation.  D Dimer is a product of fibrinolysis and was elevated.  FDPs in large quantities effectively act as pathological anticoagulant and anti-platelet agents. DIC often result in spontaneous bleeding diatheses and supportive treatment with transfusions of blood products are usually ineffective. Fortunately, in this case, there were no obvious bleeding diathesis observed such as petechiae, bruising or prolonged oozing after venepunctures. Nevertheless, fresh frozen plasma was given to reduce bleeding risks.

DIC can also cause organ dysfunction due to vascular thrombosis, haemorrhage or hypoperfusion. For RA, she showed evidence of acute kidney injury, high serum lactate levels and retiform purpura of her distal lower extremities on Day 2 of admission. Microangiopathic Haemolytic Anaemia (MAHA) is milder in DIC compared to other thrombotic microangiopathies. This patient had evidence of MAHA as suggested by elevated LDH, haptoglobin and blood film findings of schistocytes and helmet cells.

This case illustrates the challenges of managing VTE with concomitant DIC. Traditionally, first-line treatment for DVT or Pulmonary Embolism (PE) in a hemodynamically stable patient is therapeutic anticoagulation. However, in RA’s case therapeutic anticoagulation was contraindicated due to significant thrombocytopenia and abnormally prolonged clotting times. These were indications of high bleeding risk, and her clotting times and platelet counts remained abnormal despite symptomatic support with blood products.

Thrombolysis may be considered for patients with submassive PE and low bleeding risk [6]. However, thrombolytic therapy achieves only clot lysis at the expense of increased bleeding risk but has no impact on long term outcomes like mortality or recurrence of DVT when compared to anticoagulant [7]. Hence systemic thrombolysis is not routinely recommended for treatment of DVT.  Thrombolysis was also unsuitable due to high bleeding risk from underlying DIC [8]. RA’s deterioration occurred suddenly with drop in BP and oxygen saturation. Despite supportive treatment with IV fluid boluses and supplemental oxygen, her vital signs did not improve. There would not have been adequate time to administer the full thrombolytic dose as the massive PE blocked both her pulmonary arteries with evidence of right heart strain [9].

Saddle embolus which causes massive PE is usually a rapidly fatal complication of DVT and comprises 10% of all PE cases [10]. Large enough saddle embolus obstructs both right and left pulmonary arteries, resulting in right heart failure and death.

Mechanical Thrombectomy is an option for DVT or PE in those with high bleeding risks or those who failed thrombolysis and are at low bleeding risk. It is an endovascular procedure involving catheter-directed removal of the thrombus or embolus. Various techniques are available like angioplasty, aspiration, rotational, rheolytic and ultrasound accelerated device [11-13]. A catheter is typically inserted via the right femoral vein or, if contraindicated, the right jugular vein. While primarily used for acute cerebral ischemic stroke, it can also be employed for clot retrieval in acute myocardial infarction and PE [14]. Catheter directed thrombolysis may involve infusion of thrombolytic drug directly into the thrombus. Major bleeding as a complication occurs in 3.6% of patients undergoing thrombectomy. These include intracranial bleeding, gastrointestinal bleeding, retroperitoneal bleeding and haemolytic anaemia requiring transfusion. Minor bleeding complications in 28% of patients were associated with access site bleeding [15].

Mechanical thrombectomy helps restore venous patency and reduces post-thrombotic complications. Ideally, mechanical and/or pharmacological anticoagulation should follow thrombectomy to prevent recurrence. Mechanical Thrombectomy offers significant functional benefits for young patients with acute DVT and is a superior option for managing VTE in high bleeding risk subgroups [16]. Success rate of total or near-total removal of thrombus or embolus can be up to 87% (16) and venous patency rate is 75-100% at 12 months [17].

VTE is associated with a mortality rate of 23% [18]. Untreated acute PE is associated with 30% mortality and mortality is still high at 8% even among treated PE (10). Clinicians should actively identify patients at risk for VTE and initiate mechanical and/or pharmacological prophylaxis to reduce VTE incidence [19]. Diagnosis of VTE remains challenging for most clinicians, as signs are vague. Hence, vigilance for VTE signs and symptoms is crucial, as patients can deteriorate rapidly, especially when PE occurs as a complication. Early detection and initiation of treatment is essential to prevent recurrent thrombosis and mortality [20]. Many medicolegal cases arise from delayed or missed diagnoses of VTE [21]. In cases where traditional treatment options are contraindicated, catheter directed mechanical Thrombectomy can be considered to address the limitations associated with conventional treatment options like anticoagulant therapies. This also highlights the importance of multidisciplinary management in complicated cases of VTE.