Diffuse Alveolar Hemorrhage Due to Warfarin a Case Report and Literature Review
INTRODUCTION
Diffuse alveolar hemorrhage (DAH) is a rare clinical entity which refers to haemorrhage into the acinar portion of the lung from the pulmonary microvasculature.[1] This occurs as a result of the disruption of the alveolar–capillary basement membrane, leading to the intra-alveolar collection of reddish blood cells. The prognosis of patients with DAH is often dismal, and the in-hospital bloodshed ranges widely from twenty% to 100%.[2] A strong clinical suspicion is often required for making an early diagnosis to prevent disease progression and reduce the bloodshed charge per unit.[1]
A broad spectrum of clinical conditions are known to crusade DAH. This includes immunological mediated weather condition such equally systemic vasculitis (granulomatosis with polyangitis [Wegner's granulomatosis], microscopic polyangitis), rheumatoid arthritis, systemic lupus erythematosus (SLE), antiglomerular basement membrane antibody disease (Goodpasture syndrome), antiphospholipid syndrome, and Bechet's illness. The nonimmunological mediated atmospheric condition include drugs, toxins, bleeding disorders, and malignancy.[1 iii]
Anticoagulants are increasingly beingness used in a variety of clinical atmospheric condition, and bleeding forms an important agin consequence of anticoagulant use. DAH due to warfarin is an uncommon clinical entity and has been infrequently documented in the literature.[4] The paucity of the literature on the subject prompted this report of a young male who presented with hemoptysis and was subsequently diagnosed with DAH as a consequence of warfarin therapy.
Example REPORT
A 27-twelvemonth-old, HIV-negative, never-smoker male presented to the emergency department with complaints of hemoptysis forth with shortness of jiff for the past 3 days. His clinical course was characterized by multiple bouts of coughing out vivid crimson blood around 200 ml/twenty-four hour period for 3 days. Hemoptysis was not accompanied with malena, bleeding diathesis, and gum or nasal bleed. In addition, he likewise had symptoms of dyspnea at rest, which were not associated with wheezing. One calendar month prior to presentation, he had complained of exertional dyspnea accompanied with pain and swelling in the right leg for which he underwent a computed tomography scan of the chest. At that indicate, a diagnosis of pulmonary embolism along with right lower-limb deep-venous thrombosis was made. He was started on oral anticoagulants (tablet warfarin: 5 mg/day) after an adequate overlap with low-molecular-weight heparin. Notwithstanding, the patient had been taking the drug erratically without adequate monitoring for a month prior to presentation. Full general physical exam revealed a young male in respiratory distress with a saturation of ninety% while breathing ambient room air. At that place was an asymmetry in the girth of the lower limbs, with correct limb girth being larger. Chest auscultation revealed vesicular breath sounds of equal intensity with bibasilar fine-finish inspiratory crackle.
Investigations
On admission, the hemoglobin levels were xiv.two gm% which later barbarous to ten.6 gm% over the course of 3 days. Liver and renal function tests also as the urine routine analysis were within the normal limits. The prothrombin time (PT) values done on admission were deranged with an international normalized ratio (INR) of seven.2. A review of the past records revealed PT values of 22 and an INR of 2.05 at the time of discharge. Breast radiograph washed on presentation revealed bilateral upper-zone infiltrates (right > left). Contrast-enhanced computed tomography of the breast revealed bilateral eccentric filling defects in the pulmonary artery suggestive of pulmonary thromboembolism [Figure 1a]. In addition, the high-resolution computed tomography of the chest showed bilateral upper-lobe ground-glass opacities with a mosaic attenuation pattern [Figure 1b]. Compression ultrasound (CUS) along with Doppler of the right lower limb revealed partial recanalized thrombus in the right common femoral vein with streaky irregular patchy flow. In view of the presence of diffuse alveolar infiltrates, the patient's consent was taken for a cobweb-optic bronchoscopy which revealed a normal tracheobronchial tree. Serial bronchoscopic alveolar lavage (BAL) was done from the right upper lobe, with each of the v sequential xx-mL aliquots of BAL being bloodier than the previous [Figure 2]. Cytological evaluation of the BAL sample revealed numerous brown intracytoplasmic hemosiderin pigment-laden macrophages on hematoxylin and eosin stain [Effigy 3a] and blue cytoplasmic granules on Pearls stain [Figure 3b]. Stains and cultures of the BAL were negative for Mycobacterium tuberculosis and other aerobic organisms every bit well as pathogenic fungi. Subsequent workup included a negative test for antineutrophil cytoplasmic antibodies, antinuclear antibody, antiglomerular basement membrane, and antiphospholipid antibodies. A diagnosis of anticoagulant (warfarin)-induced DAH was made based on (a) clinical presentation; (b) radiology; and confirmed on (c) BAL as well every bit BAL fluid cytology.
(a) Dissimilarity-enhanced computed tomography of the chest (mediastinal window: coronal section) showing eccentric filling defects in the correct and left main pulmonary arteries suggestive of pulmonary thromboembolism. (b) High-resolution computed tomography of the chest (lung window: axial department) showing bilateral upper-lobe footing-drinking glass opacities with a mosaic attenuation blueprint
Series broncho-alveolar lavage showing progressive hemorrhagic nature of the broncho-alveolar lavage fluid
(a) High-power view (H and E, ×40) of the patient's broncho-alveolar lavage fluid cytology specimen showing numerous dark-brown intracytoplasmic hemosiderin pigment-laden macrophages (blackness arrows). (b) High-power view (Pearls, ×40) of the patient's broncho-alveolar lavage fluid cytology specimen showing hemosiderin-laden macrophages. Hemosiderin is demonstrated every bit blue cytoplasmic granules
Direction
Warfarin was immediately stopped, and the patient was placed on loftier-menstruation oxygen and 10-mg intravenous Vitamin K injection was administered followed by transfusion of four units of fresh frozen plasma. In a couple of days, the patient had comeback in his symptoms, and he was weaned off the supplemental oxygen. A echo chest radiograph washed on twenty-four hours 4 showed clearance of the radiological opacities. As the patient was unable to afford newer oral anticoagulants, he was discharged on a lower dose of warfarin with an communication of strict INR monitoring in farther follow-ups.
Word
The clinical presentation in patients with DAH includes cough, hemoptysis, dyspnea, and chest hurting.[one] Hemoptysis may be absent in 1-third of patients with DAH.[5] Respiratory failure is usually the most severe class of presentation requiring ventilatory support and entailing high bloodshed rate. The diagnosis of DAH is mainly clinical in an appropriate setting and is normally supported by radiological and bronchoscopic findings.[three] Clinical history forms an important diagnostic armamentarium in patients with DAH, equally apart from establishing a diagnosis, it ofttimes elicits the etiology. Radiological features in DAH are usually nonspecific and include patch/diffuse ground-glass opacities, "crazy-paving" blueprint, or frank consolidation. These findings are frequently seen in acute pulmonary edema, acute respiratory distress syndrome (ARDS), congestive heart failure, and infections.[one] BAL often confirms the diagnosis based on (1) progressively bloodier return on sequential BAL samples and (two) hemosiderin-laden macrophages on BAL cytology.[one iii]
Based on the histological pattern, the causes of DAH may be grouped as: (1) those associated with pulmonary capillaritis; (two) associated with bland pulmonary hemorrhage; and (three) associated with diffuse alveolar impairment.[i] Pulmonary capillaritis refers to the neutrophilic infiltration of the pulmonary capillaries leading to loss of structural integrity and bleeding into the alveolar spaces. This is usually seen in DAH associated with systemic vasculitis, Goodpasture syndrome, rheumatoid arthritis, some drugs (diphenylhydantoin, propylthiouracil, and all–trans-retinoic acid), and the rare entity of idiopathic pulmonary capillaritis. In patients with bland pulmonary hemorrhage, at that place occurs bleeding into the alveolar spaces without affecting the interstitial compartment. This is often seen in patients with mitral stenosis, bleeding disorders, and anticoagulant therapy. Diffuse alveolar damage is usually seen in patients with SLE, cytotoxic drug intake, and ARDS.[half-dozen]
Anticoagulant-induced DAH is a rare clinical entity and has been infrequently documented in the medical literature. Warfarin is a Vitamin K adversary and a very strong and widely used anticoagulant. Systemic haemorrhage is oft an important complexity with warfarin therapy.[7] The risks of haemorrhage further increase because factors such as diet, concurrent medications, poor compliance, and alcohol consumption lead to fluctuating INR levels.[8] A search of the literature using PubMed, Cochrane, IndMed, Google, and other databases with the keywords "warfarin," "acenocoumarol," "Vitamin K antagonist," and "diffuse alveolar haemorrhage" revealed 18 studies[4 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25] documenting 22 patients, which has been depicted in Table 1. Brown et al.[9] in 1965 for the commencement time reported DAH caused due to warfarin in a 64-twelvemonth-one-time male who presented with hemoptysis and hematuria. He had accidentally ingested 35 mg of warfarin leading to DAH, a diagnosis of which was made clinicoradiologically. Nearly, a decade subsequently, Finley et al.[10] reported three patients with warfarin-induced "occult pulmonary hemorrhage," the diagnosis of which was established on BAL. Following this, isolated reports have come upwards highlighting this rare clinical entity.[xi 12 xiii fourteen xv 16 17 18 nineteen 20 21 22 23 24 25] A recent retrospective study from Japan[24] described the clinical features and upshot of DAH caused by antithrombotic therapy. In this written report, 14/39 patients had DAH due to warfarin, with eight on monotherapy, whereas the remaining six were on other antithrombotic agents also. Of the eight patients on warfarin monotherapy, merely 4 had DAH due to the offending drug, whereas the remaining 4 had other causes too (vasculitis and eye failure).
Tabulated review of anticoagulant-induced diffuse alveolar hemorrhage
Management of warfarin-induced DAH is unremarkably supportive, with withdrawal of the offending drug being the most important treatment strategy followed by administration of Vitamin K and fresh frozen plasma which serves as an constructive antidote.[1 3 4] Since DAH is frequently a life-threatening condition, a prompt diagnosis and early on treatment is oftentimes required to decrease the mortality. Intravenous corticosteroids and ventilatory back up are often required in cases with severe hypoxemia and respiratory failure. In a recent report,[20] extracorporeal membrane oxygenation has been used every bit a bridge to therapy in astringent cases of DAH caused due to warfarin therapy with promising results.
Our example highlights two important features related to the diagnosis and direction of drug-induced DAH. Get-go, a high index of clinical suspicion is warranted for an early and prompt diagnosis equally was seen in our case. BAL is often considered to be the golden standard and was used in our case to confirm the diagnosis. 2d, DAH has a high mortality charge per unit and hence, therapy should be instituted every bit early as possible, with reversal of anticoagulation being the cornerstone of the direction strategy.
Declaration of patient consent
The authors certify that they take obtained all appropriate patient consent forms. In the grade the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to exist reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, only anonymity cannot exist guaranteed.
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Conflicts of interest
In that location are no conflicts of interest.
REFERENCES
ane. Lara AR, Schwarz MI. Diffuse alveolar hemorrhage Chest. 2010;137:1164–71
2. de Prost N, Parrot A, Picard C, Ancel PY, Mayaud C, Fartoukh Chiliad, et al Diffuse alveolar haemorrhage: Factors associated with in-hospital and long-term mortality Eur Respir J. 2010;35:1303–eleven
three. Park MS. Diffuse alveolar hemorrhage Tuberc Respir Dis (Seoul). 2013;74:151–62
- Cited Here
4. Waness A, Aldabbagh T, Harakati K. Diffuse alveolar haemorrhage secondary to warfarin therapy for atrial fibrillation: A instance written report and literature review BMJ Case Rep 2009. 2009:pii: bcr0820080757
- Cited Hither
5. Zamora MR, Warner ML, Tuder R, Schwarz MI. Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival, and outcome Medicine (Baltimore). 1997;76:192–202
half dozen. Newsome BR, Morales JE. Lengthened alveolar hemorrhage Southward Med J. 2011;104:269–74
7. Hamby L, Weeks WB, Malikowski C. Complications of warfarin therapy: Causes, costs, and the role of the anticoagulation dispensary Eff Clin Pract. 2000;3:179–84
- Cited Here |
- PubMed
8. Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin apply: A prevalent agin outcome resulting in regulatory action Arch Intern Med. 2007;167:1414–nine
ix. Dark-brown OL, Garvey JM, Stern CA. Roentgenogram of the calendar month Breast. 1965;48:525–6
ten. Finley TN, Aronow A, Cosentino AM, Golde DW. Occult pulmonary hemorrhage in anticoagulated patients Am Rev Respir Dis. 1975;112:23–9
- Cited Here |
- PubMed
11. Granthil C, Colavolpe C, Houvenaeghel M, François G. Occult intrapulmonary hemorrhage caused by anticoagulants Ann Anesthesiol Fr. 1981;22:53–half dozen
- Cited Here |
- PubMed
12. Barnett VT, Bergmann F, Humphrey H, Chediak J. Lengthened alveolar hemorrhage secondary to superwarfarin ingestion Chest. 1992;102:1301–2
13. Erdogan D, Kocaman O, Oflaz H, Goren T. Alveolar hemorrhage associated with warfarin therapy: A case report and literature review Int J Cardiovasc Imaging. 2004;20:155–9
14. Thomas JK, Jayaprakash K, Misiriya KJ, Khadar SA, Pappachan JM. Catastrophic pulmonary alveolar hemorrhage complicating warfarin therapy J Assoc Physicians India. 2008;56:34
- Cited Here |
- PubMed
15. Klenner AF, Friesecke Due south, Schäper C, Ewert R, Gläser South. Lengthened alveolar hemorrhage with acute respiratory distress syndrome associated with phenprocoumon therapy Blood Coagul Fibrinolysis. 2008;19:813–five
xvi. Mogili South, Krishnamurthy M, Alkhoury Z, Lyons J. Warfarin induced intra alveolar hemorrhage: A case report Internet J Intern Med. 2009;viii:1–3
17. Yardan T, Erenler AK, Genç S, Akdemir HU. A case of diffuse alveolar hemorrhage due to uncontrolled warfarin therapy JAEM. 2012;11:130–two
- Cited Here
xviii. Itoh M, Oh-Ishi S, Nemoto Yard, Senba Due south, Adachi H, Kishi K, et al A case of lengthened alveolar hemorrhage associated with tegafur plus uracil and warfarin therapy Clin Med Insights Instance Rep. 2011;iv:73–7
- Cited Hither
19. Baba M, Barnes D, Ori C. 85-twelvemonth-old patient with acute shortness of jiff Exhale. 2012;9:143–6
- Cited Here
20. Lee JH, Kim SW. Successful direction of warfarin-exacerbated diffuse alveolar hemorrhage using an extracorporeal membrane oxygenation Multidiscip Respir Med. 2013;8:16
- Cited Here
21. Uysal E, Çevik Due east, Solak S, Acar YA, Yalimol Thousand. A life-threatening complication of warfarin therapy in ED: Lengthened alveolar hemorrhage Am J Emerg Med. 2014;32:690.e3–4
22. Kaya B, Yildiz I, Baha RM, Zeytun NE, Yetisgen A. Diffuse alveolar hemorrhage associated with warfarin therapy Example Rep Med. 2015;2015:350532
- Cited Here
23. Heffler E, Campisi R, Ferri S, Crimi N. A encarmine mess: An unusual case of diffuse alveolar hemorrhage because of warfarin overdose Am J Ther. 2016;23:e1280–3
24. Otoshi T, Kataoka Y, Nakagawa A, Otsuka G, Tomii 1000. Clinical features and outcomes of diffuse alveolar hemorrhage during antithrombotic therapy: A Retrospective cohort study Lung. 2016;194:475–81
25. D'Amore K, Traficante D, McGovern T, Propersi Yard, Barnes S. An unusual consolidation: Lobar pulmonary hemorrhage due to antithrombotic therapy Clin Pract Cases Emerg Med. 2017;one:337–9
- Cited Here
Keywords:
Bronchoscopic alveolar lavage; computed tomography of the chest; diffuse alveolar hemorrhage; fiber-optic bronchoscopy; warfarin
Source: https://journals.lww.com/lungindia/Fulltext/2019/36060/Warfarin_induced_diffuse_alveolar_hemorrhage__Case.10.aspx
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