Thrombotic storm refers to a clinical presentation of acute development of multiple thromboembolic events involving diverse vascular beds [18]. Affected individuals are typically young, and thromboembolic events often involve unusual sites [18, 19]. The term “thrombotic storm” was first used by Kitchens in 1998, and then the clinical phenotype was proposed by a multidisciplinary group for clinical studies. The characteristics of thrombotic storm include (a) an underlying hypercoagulable state; (b) a provocative factor or “trigger” associated with initiation; (c) new thromboembolic events developing rapidly, especially if therapy is delayed; (d) importance of prompt initiation of antithrombotic therapy ; and (e) good long-term prognosis, if the cycle of thrombosis is interrupted early. Of the six patients in Kitchen’s report, three likely had CAPS [20].

In addition to CAPS, several disorders are included under the umbrella of thrombotic storm including [21] atypical presentations of thrombotic thrombocytopenic purpura (TTP), in which thrombotic occlusions may develop days to weeks before the development of thrombocytopenia and characteristic microangiopathic changes [22, 23]. Catastrophic thrombosis occurs in patients with cancer; the combination of CAPS and malignancy has been described in several patients. Recurrent thromboembolic events and antibodies against platelet factor 4/heparin complexes have been described, despite no recent exposure to heparin, an entity referred to as spontaneous heparin-induced thrombocytopenia (HIT) [24]. A small subset of patients with thrombotic storm have no recognized associated hypercoagulable states, a condition referred to as “idiopathic” thrombotic storm [21].

The initial diagnostic evaluation of a patient presenting with multiple thrombotic events includes imaging studies to define the location and extent of thrombotic occlusions, which may guide subsequent targeted therapeutic interventions and laboratory studies that include a complete blood count and blood film, screening coagulation studies (prothrombin time, activated partial thromboplastin time [aPTT], and fibrinogen), a metabolic profile, and testing for aPL. For patients in whom the initial assessment raises concern for occult malignancy, additional diagnostic imaging and/or laboratory studies should be obtained to confirm the diagnosis [25].

Therapeutic anticoagulation must be initiated promptly, as new thromboses occur rapidly. Unfractionated heparin is an effective anticoagulant in this setting, given the ability to titrate dose, familiarity with management in the periprocedural setting, and availability of a reversal agent (which should be reserved for cases of disastrous hemorrhagic complications only). A parenteral direct thrombin inhibitor, such as argatroban and bivalirudin, can be used if there has been relatively recent exposure to heparin and delayed HIT is in the differential diagnosis. Low molecular weight heparin is effective in the majority of patients with multiple thromboses and malignancy, assuming normal renal function.

Many patients will have thrombocytopenia on presentation. If review of the peripheral blood film by the hematologist reveals schistocytes, the patient most likely has a thrombotic microangiopathy, such as TTP or CAPS. A prolonged aPTT may suggest the presence of an aPL, but this needs to be further evaluated with additional laboratory testing. If either diagnosis is suspected, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) level should be sent and plasma exchange should be initiated; a diagnosis of TTP is supported by a markedly decreased ADAMTS13 level (e.g., <5%). Corticosteroids are also commonly administered to patients with CAPS [17] as well as acquired (autoantibody mediated) TTP [26].

Patients with a new or unexpected thrombocytopenia on presentation in the absence of a microangiopathic hemolytic anemia, or who rapidly exhibit a drop in the platelet count after heparin is initiated, may have an unusual presentation of HIT, referred to as spontaneous HIT [24]. Laboratory testing for anti-platelet factor 4/heparin antibodies should be sent, and the patient should be switched to an alternative anticoagulant, either a parenteral direct thrombin inhibitor or fondaparinux .

If the prothrombin time (PT) is also prolonged, and/or the fibrinogen level is decreased, the possibility of a consumptive process, such as DIC, needs to be considered. Depending on the severity of the coagulopathy, DIC can complicate safe administration of anticoagulant therapy [21]. Another cause of an elevated PT is antibody to prothrombin, which sometimes accompanies aPL, whether or not the patient has CAPS. If this antibody is the cause, corticosteroid therapy is indicated.

The current recommendations for the treatment of CAPS are based on the following steps: