With worsening of his hemorrhagic infarct, along with his low platelet count and negative HIT panel,the decision was made to transfuse 2 units of platelets. His platelet count increased to 64,000 cells/mm3 after transfusion, subsequently dropping to 44,000 cells/mm3. However, during this time, the patient began to have worsening right lower extremity pain and left upper quadrant abdominal pain.
A CT scan of the thorax showed multifocal right hilar adenopathy suspicious for malignancy, either metastatic or representing a central lung carcinoma. It also showed nonocclusive segmental and possibly subsegmental pulmonary emboli in the right lower and middle lobes, as well as hypodense areas in the spleen, suggestive of areas of splenic infarction. Echocardiography showed an ejection fraction of 60%–70%, diastolic dysfunction, mildly elevated pulmonary artery pressure, and no evidence of patent foramen ovale.A cardiac stress test showed no reversible defects and an ejection fraction of 63%.
Risk of further bleeding into the brain was thought to be too great to initiate anticoagulation despite the CT thorax findings. The neurologist recommended waiting 2 weeks post hemorrhagic infarction before beginning anticoagulation. Antiphospholipid antibody syndrome was ruled out, with a negative lupus anticoagulant and anticardiolipin antibody. Also, negative blood cultures, normal fibrinogen levels, and normal haptoglobin levels ruled out disseminated intravascular coagulation. D-dimer was elevated but nonspecific, secondary to malignancy and multiple infarcts. He was started on aspirin (81 mg daily) 9 days after admission.
The patient had a repeat CT scan of the thorax and CT scan of the abdomen and pelvis due to continued abdominal pain. The CT scans showed multiple subsegmental pulmonary emboli, greatest in the right lower lobe, some of which were new since the prior study; continued evidence of multifocal splenic infarction (Figure 3); and multiple right and left kidney infarcts.
The patient then underwent endobronchial ultrasound (EBUS)-guided biopsy of his right hilar adenopathy to confirm the diagnosis of suspected malignancy. After the procedure, he developed right upper quadrant pleuritic pain with a low-grade fever. A repeat CT scan of the thorax showed a marked increase in the extent of the right lower lobe pulmonary emboli, with a new small embolus noted in the anterior segment of the right upper lobe. There was a thrombus inferior to the IVC filter, with probable mild extension of a thrombus superior to the filter as well, and again multiple splenic and bilateral renal infarcts.
With progression of thrombosis and now post EBUS, anticoagulation was initiated with argatroban and warfarin. His D-dimer was followed daily and remained high, despite therapeutic anticoagulation with warfarin. Given the persistently elevated D-dimer, the hematologist recommended discontinuing warfarin and starting fondaparinux (Arixtra) subcutaneously. His platelet count improved to a range of 156,000 cells/mm3 to 181,000 cells/mm3, even before the initiation of chemotherapy.
Follow-up
HIT was suspected clinically by classic drop in platelet count but was negative on enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). The patient has been maintained on fondaparinux for anticoagulation, avoiding heparin. Factor V Leiden and lupus anticoagulant were negative.
Fondaparinux was discontinued after 3 months, and the patient presented again with swelling of his right lower extremity. Ultrasonography of the right lower extremity redemonstrated an occlusive thrombus in the peripheral portion of the right femoaral vein and throughout the right peroneal vein. The patient was restarted on fondaparinux (7.5 mg subcutaneously daily). During this follow-up, his platelet count ranged from 134,000 cells/mm3 to 193,000 cells/mm3.
Regarding management of nonsmall cell lung carcinoma of the left upper lobe (stains positive for TTF- 1 [thyroid transcription factor-1], CK7, and CK20; weakly positive for CK5/6; and negative for P63) with metastasis to bone and adrenal glands, he received 4 cycles of paclitaxel/carboplatin, with improved disease. A repeat CT of the chest, abdomen, and pelvis after chemotherapy showed improvement in mediastinal and hilar lymphadenopathy, resolution of extensive right lower lobe pulmonary consolidation, resolution of right-sided effusion, and no evidence of metastatic malignancy in the abdomen or pelvis and no osseous metastasis.
He was started on maintenance therapy with pemetrexed (Alimta), which was continued for 4 months, until repeat CT revealed progressive disease. He then received 4 cycles of vinorelbine. He had progression-free survival of 7 months from first-line chemotherapy and stable disease for 7 months after 4 cycles of vinorelbine.
Discussion
In summary, we have a 73-year-old man admitted with a hemorrhagbic infarct, NSTEMI, and recently diagnosed right lower extremity DVT with a decreasing platelet count in the setting of LMWH. Throughout the hospital course, he had worsening hemorrhagic infarcts, preventing proper anticoagulation for his progressive thromboembolic events in the lungs, spleen, kidneys, and legs. Incidentally, he was also found to have a mass on a chest x-ray, later identified by biopsy as adenocarcinoma.