CLINICAL PRACTICE

Unexpected hemorrhage: An unusual and potentially catastrophic clinical challenge Angela Y. Lambing, MSN, ANP-C, GNP-C (Nurse Practitioner Coordinator) Department of Hematology and Oncology, Hemophilia and Thrombosis Treatment Center, Henry Ford Health System, Detroit, Michigan

Keywords Autoimmune disorders; nurse practitioner communication; hematology; hemophilia; cancer. Correspondence Angela Y. Lambing, MSN, RNCS, NP, Department of Hematology and Oncology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48201. Tel: (313) 916-9094; Fax: (313) 916-9047; E-mail: [email protected] Received: November 2010; accepted: August 2011 doi: 10.1111/j.1745-7599.2012.00807.x Disclosures This manuscript was prepared with editorial assistance provided by Jeffrey M. Palmer, PhD, ETHOS Health Communications, Newtown, Pennsylvania, with financial assistance from Novo Nordisk, Inc., in compliance with international Good Publication Practice guidelines.

Abstract Purpose: Unexpected bleeding or hemorrhage related to the development of acquired factor VIII inhibitors is an emerging clinical challenge in patients. Symptoms can occur suddenly with bleeding and/or bruising that is excessive relative to the degree of injury or severity of a comorbid condition. Diagnosis is difficult, and bleeding can quickly become life threatening if not treated promptly. This review provides current information, using a patient case scenario, to improve awareness and recognition of patients presenting unexpectedly with excessive bleeding of unknown etiology. Data sources: To complete this review, a search of English-language publications was conducted using Medline and CINAHL databases (1966–2010). Conclusions: Although development of acquired factor VIII inhibitors is rare, its incidence is increasing in many different patient care settings. Improved awareness and recognition is needed to mitigate the significant patient morbidity and mortality that can occur without rapid and timely treatment by experienced hematology specialists. Implications for practice: Nurse practitioners, as front-line clinicians treating patients in various therapeutic areas, may be the first healthcare professionals who see patients with this disorder. Increased knowledge and awareness of this rare but potentially catastrophic cause of excessive bleeding can improve prompt treatment and optimize patient outcomes.

Introduction Unexpected bleeding or hemorrhage that occurs suddenly in patients without a personal or family history of bleeding problems is a significant clinical challenge, especially in an aging patient population with comorbid diseases or conditions (Franchini, Gandini, Di Paolantonio, & Mariani, 2005; Kessler, 2008; Tufano et al., 2010). An acute case of unexpected bleeding that is unrelated to a surgical procedure performed, the degree of an injury, or the severity of a disease state or other medical condition, can be difficult to diagnose (Franchini et al., 2005; Kessler, 2008). Unexplained excessive bleeding can quickly escalate and become life threatening if not promptly recognized and appropriately treated (Franchini et al., 2005; Franchini & Lippi, 2009). The acute onset of unexplained bleeding, similar to that which is described

342

in the patient scenario presented after this section, should trigger suspicion of an acquired bleeding diathesis, which may involve a new previously undiagnosed clotting factor deficiency or an inhibitor based on a combination of clinically recognized signs and symptoms (Table 1). Unexplained bleeding or hemorrhage may result from abnormalities of one or more components of the coagulation cascade, including platelets, coagulation factors, and endothelial cells in the vasculature (Drews, 2003; Green, 2007; Levi & Opal, 2006). In a patient with no previous history of bleeding, diagnosis can be challenging and may be delayed because of the interplay of a number of different coagulation molecules and cellular components (Franchini et al., 2005; Franchini & Lippi, 2008; Kessler, 2008). Abnormal bleeding may be caused by thrombocytopenia, coagulation factor deficiencies, or altered tissue factor expression on circulating and endothelial cells

C 2012 The Author Journal of the American Association of Nurse Practitioners 25 (2013) 342–350   C 2012 American Association of Nurse Practitioners

Unexpected hemorrhage

A. Y. Lambing

Table 1 Signs and symptoms that should raise suspicion of an acquired

Table 2 Conditions or risk factors associated with acquired factor VIII

bleeding diathesis

inhibitorsa

1 – Bleeding or hemorrhage that is excessive relative to the degree of injury or severity of disease. 2 – Unusual location of bleeding or hemorrhage (i.e., skin, muscle, soft tissues, mucosal tissues). 3 – An isolated, prolonged aPTT. 4 – No previous personal or family bleeding history. 5 – A variable bleeding pattern. 6 – A primary disease state, condition, or drug therapy associated with inhibitor development.

Comorbid conditions or disease states with inhibitor risk Autoimmune disease

Note: aPTT, activated partial thromboplastin time.

(Drews, 2003; Levi & Opal, 2006). Unexplained bleeding may also occur as the result of sepsis, disseminated intravascular coagulation, massive blood loss, transfusions, drug reactions or heparin overdose, circulating antiplatelet antibodies, and impaired coagulation factor synthesis (Drews, 2003; Franchini et al., 2007; Levi & Opal, 2006). Neutralizing inhibitors directed against a specific coagulation factor can produce persistent bleeding or hemorrhage because of decreased plasma factor levels that can impair clotting. Autoantibodies generated against key coagulation factors are commonly referred to as acquired inhibitors. Factor VIII (FVIII) plays a pivotal role in the function of the coagulation pathway and control of hemostasis, and is one of the most commonly targeted pathways of inhibitor formation (Ghosh & Shetty, 2009; Holme, Brosstad, & Tjonnfjord, 2005; Ma & Carrizosa, 2006). Acquired FVIII inhibitors can occur spontaneously (i.e., idiopathic) or in association with numerous disease states, specific medical conditions, and use of certain pharmacologic agents (Table 2; Franchini et al., 2005). Though rare, the risk of occurrence of acquired FVIII inhibitors is widespread across many different patient populations, making it an emerging bleeding threat that poses debilitating and even catastrophic consequences within days or weeks, if not appropriately diagnosed and rapidly treated (Bitting, Bent, Li, & Kohlwes, 2009; HuthKuhne et al., 2009; Kessler, 2008). This bleeding disorder ¨ may present in a wide variety of settings relevant to nurse practitioners (NPs), including the emergency department, acute care clinic, primary care setting, ob/gyn practice, the operating room, and intensive care, to name a few. Nurse practitioners, among other healthcare professionals, should be concerned because as front-line clinicians caring for diverse patient populations, it is imperative that they be aware of the signs, symptoms, and risk factors for this uncommon yet serious bleeding diathesis. Prompt recognition and diagnosis are essential to ensure that

Blood transfusions Dermatologic disease Diabetes Hepatitis Inflammatory bowel disease Malignancy—Hematologic

Solid tumors

Pregnancy Respiratory diseases Surgical procedures

r Goodpasture syndrome r Graves disease r Hemolytic anemia r Hypothyroidism r Multiple sclerosis r Myasthenia gravis r Rheumatoid arthritis r Sjogren ¨ syndrome r Systemic lupus erythematosus r Temporal arteritis r Transfusion reactionsb r Traumac r Pemphigus r Psoriasis r Type 1d r Acute hepatitis B r Acute hepatitis C r Crohn’s diseasee r Ulcerative colitis r Chronic lymphocytic leukemia r Erythroleukemia r Multiple myeloma r Myelodysplastic syndrome r Myelofibrosis r Non-Hodgkin lymphoma r Cutaneous T-cell lymphomaf r Waldenstrom macroglobulinemia r Bile duct r Breast r Cervix r Colon r Head and neck r Kidney r Lung r Melanoma r Pancreas r Prostate r Stomach r Postpartumg r Asthma r Chronic obstructive pulmonary disorder r Clinically silent inhibitorsh r Paraneoplastic factorsi Continued

343

Unexpected hemorrhage

A. Y. Lambing

Table 2 (Continued) Comorbid conditions or disease states with inhibitor risk Medications Drug induced

r Bacille Calmette–Guerin ´ vaccination r Chloramphenicol r Depot thioxanthene r Fludarabine r Interferon-alpha r Methyldopa r Paclitaxelj r Penicillin and derivatives r Phenytoin r Sulfamides

a

Table adapted with permission from Franchini et al. (2005). (Delgado et al., 2003). c (Chen et al., 2004). d (Wajima & Hall, 1989). e (Kyriakou et al., 2002). f (Waddell, Lehane, & Zubler, 1981). g (Franchini, 2006). h (Baudo & de Cataldo, 2004). i (Franchini et al., 2008; Green, 2007). j (El-Osta, Reddy, & Deutsch, 2009). b

appropriate therapeutic strategies are initiated to effectively manage patients with acquired FVIII inhibitors (Franchini & Lippi, 2008, 2009; Kessler, 2008). From the search and review of the literature, the availability of published peer-reviewed clinical research articles or evidence-based reviews within the NP literature regarding acquired FVIII inhibitor-mediated bleeding and hemorrhage is limited. This article reviews the evolving epidemiology and latest knowledge regarding the clinical presentation, diagnosis, and appropriate management of acquired FVIII inhibitors in various patient care settings in which NPs are most likely to encounter this bleeding disorder. To complete this review, a search of English-language publications was conducted through Medline and CINAHL databases (1966–2010). Each search consisted of specific keywords or combinations of keywords and included “acquired coagulopathy,” “unexplained hemorrhage,” “acquired factor VIII inhibitors,” “acquired hemophilia A,” “acquired bleeding disorders,” “factor VIII inhibitors,” and “primary care,” “nursing,” or “nursing management.”

Patient clinical scenario A 70-year-old man diagnosed with colon cancer underwent surgery for a colectomy with a colostomy. Prior to surgery his coagulation profile (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) were 344

normal. On postoperative day 1, his aPTT was 44 s (normal, 26–36 s). Subsequent aPTT levels on postoperative days 2 and 3 were 50 and 58 s, respectively. His surgical recovery was otherwise unremarkable. He was discharged after a 5-day inpatient hospital stay. He returned 3 weeks later with bleeding from his colostomy. The patient had a history of extensive coronary and peripheral artery disease and degenerative joint disease, but no prior history of bleeding problems. A laparotomy was performed to evaluate and repair a suspected anastomosis leak. No leak was identified. Four days after surgery, blood was observed in his nasogastric drainage. The patient’s hemoglobin levels had dropped, prompting transfer to the intensive care unit. The patient required intravenous infusions of fresh frozen plasma, platelets, and packed red blood cells. His aPTT was noted to have increased from 77 to 92 s and there was now significant oozing of blood from an arterial line. Further testing showed the patient’s aPTT remained elevated at 77 s; however, his PT was normal. Other laboratory values were within normal ranges, including bleeding time (6 min 42 s; normal

Unexpected hemorrhage: an unusual and potentially catastrophic clinical challenge.

Unexpected bleeding or hemorrhage related to the development of acquired factor VIII inhibitors is an emerging clinical challenge in patients. Symptom...
203KB Sizes 0 Downloads 0 Views