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Thrombosis is a common complication in patients with cancer and it is estimated that about 20% of patients with cancer experience venous thromboembolism (VTE). This complication is associated with high rate of morbidity and mortality and is sometimes the first manifestation of an occult cancer. The risk profiles and markers involved in cancer-associated thrombosis share similarities with inflammation-induced atherosclerosis and thrombosis. The type of cancer, chemotherapy, surgery, central venous catheters, pre-chemotherapy platelet and leukocyte count are associated with high risk of VTE in cancer patients. Landmark studies demonstrated that effective prophylaxis and treatment of VTE reduced morbidity and increased survival. Low-molecular-weight heparin (LMWH) is preferred as an effective and safe means for prophylaxis and treatment of VTE. It has largely replaced unfractionated heparin and vitamin K antagonists. The advantages of LMWH include increased survival and quality of life, decreased rate of VTE, low incidence of thrombocytopenia. New guidelines for prophylaxis and treatment are now available and prophylaxis is recommended in hospitalized cancer patients and patients undergoing major surgery. Treatment with LMWH should be considered as the first line of therapy for established VTE and to prevent recurrent thrombosis in patients with cancer.

Current concepts of the etiology, pathophysiology, clinical and laboratory diagnosis and management of fulminant and low-grade disseminated intravascular coagulation (DIC) have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding the pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Objective clinical and laboratory criteria for diagnosis of DIC have been delineated, thus avoiding needless confusion and empirical decisions regarding the diagnosis. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Also presented are clear criteria for severity of DIC and objective criteria for defining a response to therapy. Also, since it is often difficult for the individual physician to decide when to stop expensive therapy, objective criteria by which therapy may be stopped when continuation is likely fruitless are presented as a guideline.

As outlined in this review, patients with cancer may harbor many alterations of hemostasis. These are multifaceted and must be taken into account when trying to control hemorrhage or thrombosis in cancer patients. Often, hemorrhage or thrombosis is the final fatal event in many patients with metastatic solid tumor or hematologic malignancies. Patients with malignancy present a major clinical challenge in this new era of oncologic awareness and more aggressive care, which has led to prolonged survival for patients and a longer time frame during which these complications may develop. Therefore, these complications are occurring more commonly. It is important to realize that these alterations of hemostasis exist and must be approached in a sequential and logical manner with respect to diagnosis; only in this way can responsible, efficacious, and rational therapy be delivered to patients. By far the most common alteration of hemostasis in malignancy is that of hemorrhage associated with thrombocytopenia, either drug-induced, radiation-induced, or from bone marrow invasion. However, hemorrhage resulting from DIC is also quite common and may present as hemorrhage, thrombosis, thromboembolus, or any combination thereof. Many antineoplastic drugs and radiation therapy may lead to or significantly enhance hemorrhage in patients with malignancy. Thrombosis, also commonly seen in patients with malignancy, is often a manifestation of low-grade DIC, conspicuous as an intravascular thrombotic or thromboembolic event instead of an intravascular proteolytic (hemorrhagic) event. When suspecting this, confirmatory laboratory evidence must be sought and the patient treated appropriately. When approaching the patient with malignancy and either hemorrhage or thrombosis, all the potential defects in hemostasis must be taken into account, defined from the laboratory standpoint, and treated in as precise and logical manner as possible.

Current concepts of the many complex pathophysiological mechanisms and clinical and laboratory manifestations of disseminated intravascular coagulation (DIC) are presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Many therapeutic decisions are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. The future holds promise for not only newer antithrombotic agents, but also agents which will block, blunt or modify cytokine activity and the activity of vasoactive substances. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and hemodynamic and other clinical parameters.

Disseminated intravascular coagulation (DIC) is being recognized with increased frequency and not only are newer diagnostic modalities becoming available for this syndrome, but newer, some controversial, methods of management are also being recognized and may prove to increase survival in DIC. In addition, several syndromes classically considered separate, definitive disease entities, may actually share similar or identical pathophysiology to DIC. This review summarized current, as well as controversial aspects of etiology, pathophysiology, clinical and laboratory diagnosis, and management of DIC. In addition, a brief discussion of syndromes which may share similar or identical pathophysiology to DIC is included.

ACAs and the lupus anticoagulant are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism or mechanisms whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories, as previously discussed, have been advanced. The most common thrombotic events associated with ACAs are DVT and PE (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), cerebrovascular or retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). The relative frequency of ACAs in association with arterial and venous thrombosis strongly suggests that these should be looked for in any patient with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through IV) should be defined, if possible, because this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACAs, patients with primary lupus anticoagulant thrombosis syndrome usually have venous thrombosis. Since the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with ACAs, definitive tests (ELISA for ACA and the dRVVT for lupus anticoagulant) should be immediately ordered when suspecting antiphospholipid syndrome or in patients with otherwise unexplained thrombotic or thromboembolic events.

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