Figure 1A, B: Axial Thoracic Imaging by Computed Tomography Imaging at Diagnosis. A, Right Ventricle Thrombus (Red Arrow). B, Right Atrial Thrombus (Red Arrow).

Figure 2: Axial Abdominal Imaging by Computed Tomography Imaging at Diagnosis, Exophytic Right Renal Mass (Red Arrow).

He was hospitalized to establish a final diagnosis and treatment. Anticoagulant therapy was recommended for pulmonary embolism and cardiac thrombus in the consultation of cardiology and chest diseases. He had an initial white blood cell (WBC) of 13,800 /uL, hemoglobin (Hgb) of 8 g/dl (from 11.1 to 17.1), platelet count of 34x103/uL (150-400), reticulocyte count of 185.9x10⁹ /L (40-70), fibrinogen of 267.38 mg/dl, international normalized ratio (INR) of 1.22, prothrombin time (PT) of 15.2 sec (from 10 to 14), activated partial thromboplastin time (aPTT) of 32 sec, D-dimer of >7.5 mg/L (0-0.55), and LDH of 1443 u/L (120-246) (Table 1).

Table 1: Laboratory findings and blood drawn at admission.

He consulted with the hematology department to assess for potential DIC. Clinical and physical examination showed low procalcitonin and no signs of active inflammation. Therefore, the possibility of infection was ruled out. Schistocytes and thrombocytopenia were observed in the peripheral smear. He had a score of 6 on the International Society on Thrombosis and Hemostasis (ISTH) diagnostic scoring system for DIC, and therefore, was diagnosed with DIC due to malignancy⁷. Treatment targeted at the underlying disease or plasmapheresis was recommended. In the follow-up, the patient whose platelet count values were between 20-29x10³/uL was recommended by the hematology, instead of plasmapheresis, underlying disease treatment, when platelet count was between 30-50x10³, enoxaparin sodium subcutaneous 0.6 ml 1x1, platelet count >50 x 10³/uL, enoxaparin sodium 2x1 and platelet suspension support. However, no renal biopsy was performed because the patient had low platelet count. Instead, transbronchial biopsy was performed on the pleural lesion in the lung because he had a low risk of bleeding. In the meantime, platelet suspension was administered, and occasional hemoptysis and nosebleed were observed. During the 14-day hospitalization, the patient was administered 14 units of pooled platelet suspension and four units of apheresis platelet suspension. Fatigue and weight loss were observed in the patient during follow-up. He was pathologically diagnosed with RCC on August 29, 2019, and therefore, started to receive Pazopanib 400 mg (1x2). He had platelet count greater than 50x10³ for the first time after on September 1, 2019 and received anticoagulants twice a day without transfusion. He had an almost complete regression of hemoptysis. He had an Hgb of 11 and platelet count of 107x10³/uL on September 18, 2019. The hematology department assessed his peripheral smear. The clinical presentation, regression of thrombocytopenia, and absence of schistocytes showed that he had somewhat improved DIC. He had less shortness of breath and was prescribed enoxaparin sodium 0.6 ml (1x1) and pazopanib 400 mg (1x2) and then discharged. Two weeks later, he visited our department complaining of fatigue and weakness. He had an Hgb of 10.6 and platelet count of 103 x 10³/uL. He had had normal liver and kidney function values, and therefore, continued receiving the same treatment. He was readmitted to the emergency outpatient clinic two days after his last visit due to the worsening of hemoptysis and shortness of breath. He was hospitalized again. His platelet count dropped (platelet: 29x10³/uL) and coagulation parameters worsened (PT:18 sec, INR:1.51). He was followed up in the intensive care unit for two days and died from massive hemoptysis and respiratory failure.

For patients with surgically resectable RCC, the standard of care is partial or radical nephrectomy and surgical excision with a curative intent. However, patients with inoperable or metastatic RCC are systematically treated with target agents and/or immune control point inhibitors. RCC is very vascular, and therefore, sorafenib, sunitinib, pazopanib, axitinib, lenvatinib, and cabozantinib, which are tyrosine kinase inhibitors targeting the VEGF signaling axis, are used for first- and secondline metastatic RCC therapy^12-14. Agents targeting the mammalian target of rapamycin are used. Recent studies have focused on the combination of anti-VEGF therapy with new generation immune control point inhibitors, such as antibodies against the programmed cell death protein ligand 1 (PDL1) (avelumab and atezolizumab) and 1 (PD1) (nivolumab and pembrolizumab)¹⁵. Another combination (Checkmate 214, NCT02231749) is nivolumab with ipilimumab, the latter of which is an inhibitor of the T cell control point cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)¹⁶. This combinations are recommended at the category 1 level of the first-line therapy for metastatic RCC patients, who are at middle and high-risk. Our patient was at high risk but could not receive that combination for treatment because his health insurance did not cover it. He received Pazopanib 800 mg in the first-line therapy and tolerated it without any side effects. At first, the therapy resulted in rapid clinical improvement, however, he died from severe tumor burden and DIC at the end of the second month of treatment. One RCC patient with low tumor burden received pazopanib treatment after three cycles of chemotherapy and then were followed up in the 11th month⁶. However, another patient with severe clinical manifestation of RCC was receiving anticoagulant therapy but died four weeks after her admission before she started receiving treatment for the disease⁵. According to a study on 1117 patients with solid tumors, those with overt DIC (9 months) had significantly lower survival rates than those with non-overt DIC (14 months) (p =0.005). This indicates that serious complications, such as DIC, have a great impact on cancer outcomes⁴.

Patients with cancer may sometimes present with venous thromboembolism or pulmonary embolism before the diagnosis of cancer. However, thrombotic complications of cancer are not limited to thrombosis but may manifest themselves with other signs of procoagulant state in its most fulminant form presenting as DIC¹⁷. The clinical manifestation of DIC in cancer may be thrombosis, bleeding, or the combination of the two¹. Thrombotic microangiopathy may also occur¹⁸. Our patient was also admitted to the clinic due to bleeding and thrombosis, which are signs of a severe procoagulant state. Laboratory findings are necessary to confirm a diagnosis. Acute DIC almost always presents with thrombocytopenia and microangiopathic hemolytic anemia.

The treatment of underlying disease for DIC is the most effective approach in cancer patients. However, supportive therapy has also been used in combination with targeted therapy to prevent rapid exacerbation of coagulopathy¹⁷. Targeted therapy depends on the type of cancer. Some of the target therapies are cytotoxic chemotherapy, immunotherapy, molecularly targeted therapy, radiation therapy, endocrine therapy, and surgical therapy. Targeted therapy is the most important cancer treatment, and success in the treatment of primary disease results in withdrawal of DIC¹⁹. As for anticoagulant therapy, chemotherapy combined with low molecular weight heparin reduces the mortality rate in patients with solid tumors¹⁷. On the other hand, recombinant human soluble thrombomodulin (thrombomodulin alfa, TM-α) improves DIC scores and treats solid tumors, at least temporarily, and results in prolonged survival rate when the control of DIC and treatment of the underlying disease are compatible ²⁰. Our patient also received transfusion support and low molecular weight heparin therapy until he received treatment for the disease.