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Alveolar Hemorrhage, a Rare and Life-Threatening Complication of Catastrophic Antiphospholipid Syndrome.

1. Introduction

Antiphospholipid syndrome (APS) is a disorder that leads to a state of hypercoagulability characterized by antibodies against phospholipids resulting in thrombosis of veins or arteries. These antibodies were first described in 1906 in serological patients positive for syphilis [1].

Catastrophic antiphospholipid syndrome (CAPS) is a rare complication of APS occurring in approximately 1% of patients with a higher prevalence in women. APS is characterized by microvascular thrombosis producing multiorganic failure, the kidney being the most commonly affected organ, followed by the lungs and the central nervous system (CNS). In patients with pulmonary involvement, only 6-10% have alveolar hemorrhage which is commonly associated with microangiopathic hemolytic anemia and thrombocytopenia [2].

Certain clinical conditions may predispose to the development of CAPS including infections, malignancies, surgeries, and subtherapeutic anticoagulation. Several sets of diagnostic criteria have been proposed to stratify this rare pathology with high mortality risk. In our patients, we used the diagnostic criteria described by Asherson et al. and reviewed by Cervera et al. due to its high positive and negative predictive value. Cervera et al. acknowledge the difficulty to use biopsy to confirm occlusive microthrombi in patients in critical condition and suggest clinical and laboratory criteria to be used instead as described in Table 1. To assess and confirm thrombotic microangiopathy (TMA) in organs, we used the diagnostic workup used by Cervera et al. (Table 2) [2, 3].

The thrombotic events of this disease can occur in any blood vessel producing a wide variety of manifestations. The most common types of manifestation are associated with peripheral thrombosis (deep venous thrombosis in 38.9% of cases) and neurology (migraine 20.2% of the cases) [4].

CAPS has also been associated with pulmonary manifestations; the most common ones are acute respiratory distress syndrome, chronic thrombotic pulmonary disease, and secondary pulmonary hypertension. These manifestations are due to the disruption of the vessels surface. Alveolar hemorrhage is the rarest complication of CAPS, and it is caused by the disruption in the alveolar capillaries, leading to bleeding in the alveolar space [5, 6]. Alveolar hemorrhage's mortality rate increases from 35% in the absence of CAPS to approximately 50% in association with CAPS even in patients under treatement [7]. The clinical presentation of alveolar hemorrhage can vary from asymptomatic patients to severe respiratory failures [8]. The most frequent symptoms are dyspnea (64%), hypoxemia (55%), and cough (41%). The nonspecific nature of these symptoms urges to consider three important components in the diagnosis as the presence of blood in low respiratory tract including bloody secretion (57%), hemoptysis, or bloody secretions evidenced during tracheal aspirate or bronchoscopy, hemoglobin level below 1.5-2 g/dL with no evidence of bleeding in any other organ and no evidence of hemolysis, and diffuse infiltrate pattern in chest X-ray [8, 9].

2. Case 1

A 37-year-old female patient with APS diagnosed 17 years ago is brought to the emergency department due to syncope. The past medical history was positive for multiple transfusions due to hemolytic anemia and decreased visual acuity in recent months accompanied by continuous headaches of moderate intensity.

Laboratory tests showed anticardiolipin antibodies (ACA) IgG of 120 GPL-U/ml (positive: >10 GPL-U/ml) and IgM of 6 MPL-U/ml (negative: <7 MPL-U/ml). Severe microcytic anemia (HB: 3.6 g/dl) and thrombocytopenia require transfusion of two globular concentrates and five units of platelets. Peripheral blood smear revealed schistocytes.

Immunological tests were requested due to the suggestive autoimmune anemia, which showed positive anti-nuclear antibody, anti-RO antibody of 17IU/ml (15-25 IU/ml), C3 of 0.92 g/L (positive >0.90 g/L), C4 of 0.21 g/L (negative <0.10 g/ L), anti-thyroglobulin antibody 19.5 IU/ml (negative: <100IU/ ml), and incompatibility for all blood groups.

The patient was admitted to MICU and was placed on medium-dose corticosteroids, prophylactic anticoagulation with low-molecular weight heparins, and additional globular concentrates transfusions. Anemia was corrected with the treatment; however, the patient's condition deteriorated due to severe respiratory distress, tachypnea, hypoxia, and SO2 76%. A chest X-ray and chest CT scan showed bilateral, diffuse alveolar infiltrate (Figure 1).

Two major components of alveolar hemorrhage were evidenced in this patient: macrophages loaded with hemosiderin with macroscopic bleeding were found in bronchoscopy and severe thrombocytopenia. Despite the presence of alveolar hemorrhage, no hemoptysis was observed. Low-weight heparin was switched to unfractionated heparin, despite severe platelet disease.

Dialysis supplementation was started due to severe renal failure.

In less than seven days from the respiratory failure, the patient complained of persistent headaches. Further investigation revealed the occurrence of cerebral venous sinus thrombosis.

The patient met the criteria for definite CAPS. For these reasons, the patient was placed on enoxaparin 60 mg every 12 hours SubQ, prednisone 60 mg every 12 hours PO, and mycophenolate 2 g daily.

The patient improved and was discharged on mycophenolate and warfarin to a target INR of 3 with follow-up appointments in the outpatient clinic twelve weeks after discharge; anti-phospholipid antibody testing was repeated and confirmed the diagnosis of APS. Of note, a renal biopsy with immunofluorescence was also performed and ruled out lupus nephritis as a possible cause of renal failure.

3. Case 2

A 42-year-old female with a past medical history of rheumatoid arthritis diagnosed three months prior to admission, managed with methotrexate with poor adherence, was admitted due to psychomotor agitation without focal neurological deficits and fever (100.4[degrees]F) with neutrophilia.

Lumbar puncture showed a low glucose level in the cerebrospinal fluid (CSF) (glucose CSF 24.8 mg/dl, glucose serum: 78 mg/dl), 23 common germs in FilmArray (multiplex PCR system), as well as Gram and Chinese ink negative.

The patient lived in a tuberculosis endemic zone. Antibiotic therapy, antituberculosis drugs, and antifungal agents were initiated despite negative results.

The patient showed a sudden improvement in consciousness three days after starting treatment. However, she presented a new episode of altered mental status two days later, and it was associated with transaminases elevation 100 times above the reference value. Liver enzymes remained elevated despite discontinuation of antituberculosis agents. Brain CT scan of the brain showed ischemic areas in the corpus callosum and bilateral parietal lobes.

One day later, our patient presented severe hemodynamic decompensation with metabolic acidosis, acute respiratory failure, and pancytopenia. The patient was transferred to the MICU to provide mechanical ventilation and vasopressors.

Simultaneously, a progressive drop in hemoglobin was identified, so a bronchial tract lavage (not alveolar) was performed obtaining bloody secretions. Chest X-ray showed diffuse bilateral infiltrates. Patient's critical condition disabled him to undergo chest CT scan. Autoimmune markers were requested due to the suspicion of immune alveolar hemorrhage showing anti-cardiolipin antibodies IgM 0.3 MPL-U/ml (negative: <7 MPL-U/ml), IgG 100MPL-U/ ml (POSITIVE: >17 GPL-U/ml), Anti-DNA 29 IU/ml (positive: >20 IU/ml), and both positive anti-nuclear antibodies and lupus anticoagulant. Schistocytes were identified in peripheral blood smear. There was no evidence of lupus nephritis.

The patient met the criteria for definite CAPS associated with alveolar hemorrhage. Intravenous pulses of methyl-prednisolone 1 g daily IV and enoxaparin 60 mg daily SubQ to maintain isocoagulation state due to risk of hemorrhagic conversion of ischemic strokes were added to the already placed ventilatory support. The patient's critical condition prevented her from underwent bronchoscopy or pulmonary biopsy.

Despite the initial clinical improvement, the patient died in later days due to a new deterioration of respiratory function, renal failure, and encephalopathy.

4. Case 3

A 40 year-old male patient with a past medical history of hypertension, left nephrectomy 7 years ago due to renal artery thrombosis, ischemic cerebrovascular disease, and chronic kidney disease under clinical treatment, presented to the Emergency Department complaining of sudden hemoptysis, fatigue, and dyspnea of small efforts.

In the Emergency Department, physical examination showed altered mental status with neurological deficits, crackles in lung bases bilaterally, cyanosis, and 60% oxygen saturation without supplemental oxygen.

Additionally, metabolic acidosis (pH: 7.31, pC[O.sub.2]: 25.7 mmHg, p[O.sub.2]: 31 mmHg, HC[O.sub.3]: 12.7mmol/L, EB: 36.4), severe normochromic normocytic anemia (hemoglobin: 7.72 gr/dl, hematocrit: 22.02%), and thrombocytopenia (5000 platelets) were observed with no evidence of bleeding. Schistocytes were identified in peripheral blood smear.

A chest X-ray and CT scan were performed, showing diffuse bilateral alveolar infiltrate with perihilar and basal predominance and no important involvement of apexes or periphery (Figure 2) and bilateral alveolar infiltrates in a ground-glass pattern (Figure 3). Brain CT scan showed signs of ischemic areas in the brain parenchyma.

The patient was diagnosed with diffuse alveolar hemorrhage, and further investigation of immunological markers was ordered to identify the etiology. Anti-cardiolipin antibodies IgM 0.9MPL-U/ml (negative: <7 MPL-U/ml), IgG 155GPL-U/ml (positive: >17GPL-U/ ml), ANCA-C, and ANCA-P were negative, and anti-nuclear antibodies were positive. There was no evidence of lupus nephritis.

The patient was transferred to MICU due to hemodynamic instability and need for ventilatory support. It was not possible to perform lung biopsy or bronchoalveolar lavage due to the patient's critical condition.

The patient met the criteria for probable CAPS. Enoxaparin 60 mg every 12 hours SubQ and pulses of methylprednisolone 1 g daily IV were administered. Plasmapheresis was performed with no signs of clinical improvement; therefore, the patient was switched to immunoglobulins IV showing remarkable improvement. After overcoming the critical period, the patient was kept on chronic low-molecular weight heparin anticoagulant treatment. The patient was discharged on prednisone 30 mg daily and warfarin to a target INR of 3. Twelve weeks after discharge, anti-phospholipid antibody testing was repeated and the diagnosis of APS was confirmed.

5. Discussion

We present three diagnoses of diffuse alveolar hemorrhage in patients with CAPS with nonspecific clinical presentation. In all cases, the clinical presentation was sudden and unexpected and deteriorated rapidly within a one-week period. Out of the three patients, two fully recovered while one deceased. Given the limited literature addressing the association of alveolar hemorrhage and CAPS, we compared these 3 cases treated in our hospital with cases reported in the literature (Tables 3 and 4).

The initial respiratory symptoms our patients were cough, respiratory distress, and oxygen saturation less than 85% without oxygen support and hemoptysis. Those findings are consistent with the cases reported in the literature [9]. One of our patients presented hemoptysis, a finding listed in a third of patients with alveolar hemorrhage [5, 10].

Encephalopathy is a complication in 40.2% of CAPS cases. Even though our second patient was diagnosed with meningitis due to the presence of fever and altered mental status, it is possible that the patient's clinical presentation was a complication from CAPS itself rather than an infectious condition because of negative CSF FilmArray report. We were unable to find cases with similar initial presentations in the literature.

Both radiographic and tomographic findings were consistent with those found in the literature, diffuse areas of ground-glass opacities or consolidations in chest X-rays and infiltrated patches in the tomography. In three of the reported cases, the findings were bilateral.

Alveolar hemorrhage in APS can be explained due to anti-phospholipid antibodies binding to the alveolar surface [6]. Such antibodies can be found in both asymptomatic patients and patients with nonthrombotic manifestations. Thrombotic manifestations occur in half of the patients and hemolytic anemia in one-third of patients [9, 10].

The thrombotic effect can be explained by the inhibition of anticoagulant systems, preventing the degradation of factor V and VII altering the protein C system and the inhibition of fibrinolysis [11]. Most antibodies bind to phospholipid-binding proteins expressed on cell surfaces, endothelium, and platelets, which half-explain their pathogenesis [12]. The activation of the endothelial surface transforms the vessel wall into a procoagulant surface [9,13].

Lupus anticoagulant was positive in seven out of nine patients being the most common finding. Anti-cardiolipin antibodies were present in five out of nine patients. Anti-[beta]glycoprotein (Anti-[beta]2GPI) antibodies were positive in only four of the patients [14-17]. No changes were reported in prothrombin.

The initial management of alveolar hemorrhage is ventilatory support and anticoagulation, followed by the treatment of CAPS. Anticoagulation is key in the treatment since it inhibits clot formation and promotes fibrinolysis and could also have an effect on preventing anti-phospholipid antibodies from binding to the endothelial surface [6]. Heparin use is recommended at doses that do not increase the risk of bleeding; however, there is insufficient evidence to support a dose that avoids this risk. After anticoagulation, the use of high-dose corticosteroids is necessary to act on mediators involved in CAPS. The use of cyclophosphamide is reserved for those patients with autoimmune diseases. Plasmapheresis could have a beneficial effect by removing free antibodies, as well as other mediators responsible for the pathophysiology of catastrophic APC [6, 10, 12].

Conflicts of Interest

The authors declare that they have no conflicts of interest.


[1] K. L. Whitaker, "Antiphospholipid antibody syndrome: the difficulties of diagnosis," Journal of the American Academy of Physician Assistants, vol. 30, no. 12, pp. 10-14, 2017.

[2] R. A. Asherson, R. Cervera, P. G. De Groot et al., "Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines," Lupus, vol. 12, no. 7, pp. 530-534, 2003.

[3] R. Cervera, I. Rodriguez-Pinto, and G. Espinosa, "The diagnosis and clinical management of the catastrophic anti-phospholipid syndrome: a comprehensive review," Journal of Autoimmunity, vol. 92, pp. 1-11, 2018.

[4] R. Cervera, "Antiphospholipid syndrome," Thrombosis Research, vol. 151, pp. S43-S47, 2017.

[5] M. A. Kanakis, V. Kapsimali, A. G. Vaiopoulos, G. A. Vaiopoulos, and M. Samarkos, "The lung in the spectrum of antiphospholipid syndrome," Clin Exp Rheumatol, vol. 31, pp. 452-457, 2013.

[6] L. Stojanovich, "Pulmonary manifestations in antiphospholipid syndrome," Autoimmunity Reviews, vol. 5, no. 5, pp. 344-348, 2006.

[7] P. Heeringa, A. Schreiber, R. J. Falk, and J. C. Jennette, "Pathogenesis of pulmonary vasculitis," Seminars in Respiratory and Critical Care Medicine, vol. 25, no. 5, pp. 465-474, 2004.

[8] M. S. Park, "Diffuse alveolar hemorrhage," Tuberculosis and Respiratory Diseases, vol. 74, no. 4, pp. 151-162, 2013.

[9] N. M. Kazzaz, P. Coit, E. E. Lewis, W. J. McCune, A. H. Sawalha, and J. S. Knight, "Systemic lupus erythematosus complicated by diffuse alveolar haemorrhage: risk factors, therapy and survival," Lupus Science & Medicine, vol. 2, no. 1, p. e000117, 2015.

[10] R. Cervera, J.-C. Piette, J. Font et al., "Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients," Arthritis & Rheumatism, vol. 46, no. 4, pp. 1019-1027, 2002.

[11] A. Nayer and L. M. Ortega, "Catastrophic antiphospholipid syndrome: a clinical review," Journal of Nephropathology, vol. 3, no. 1, pp. 9-17, 2014.

[12] O. Carmi, M. Berla, Y. Shoenfeld, and Y. Levy, "Diagnosis and management of catastrophic antiphospholipid syndrome," Expert Review of Hematology, vol. 10, no. 4, pp. 365-374, 2017.

[13] C. L. Aguiar and D. Erkan, "Catastrophic antiphospholipid syndrome: how to diagnose a rare but highly fatal disease," Therapeutic Advances in Musculoskeletal Disease, vol. 5, no. 6, pp. 305-314, 2013.

[14] M. Rangel, I. Alghamdi, G. Contreras et al., "Catastrophic antiphospholipid syndrome with concurrent thrombotic and hemorrhagic manifestations," Lupus, vol. 22, no. 8, pp. 855-864, 2013.

[15] N. Martis, E. Blanchouin, R. Lazdunski et al., "A therapeutic challenge: catastrophic anti-phospholipid syndrome with diffuse alveolar haemorrhage," Immunologic Research, vol. 62, no. 2, pp. 222-224, 2015.

[16] N. Hambly, S. Sekhon, and R. A. Mclvor, "Antiphospholipid antibody syndrome: diffuse alveolar hemorrhage and LibmanSacks endocarditis in the absence of prior thrombotic events," The Ulster Medical Journal, vol. 83, no. 1, pp. 47-49, 2014.

[17] V. A. Nguyen, T. Gotwald, C. Prior, G. Obermoser, and N. Sepp, "Acute pulmonary edema, capillaritis and alveolar hemorrhage: pulmonary manifestations coexistent in antiphospholipid syndrome and systemic lupus erythematosus?," Lupus, vol. 14, no. 7, pp. 557-560, 2005.

[18] T. Wan and P. Tsang, "Catastrophic antiphospholipid syndrome presenting with pulmonary hemorrhage: case report," Journal of Thrombosis and Thrombolysis, vol. 39, no. 1, pp. 68-70, 2015.

[19] T. Isshiki, K. Sugino, K. Gocho et al., "Primary antiphospholipid syndrome associated with diffuse alveolar hemorrhage and pulmonary thromboembolism," Internal Medicine, vol. 54, no. 16, pp. 2029-2033, 2015.

Grace Loza [ID], (1) Carlos Hallo [ID], (2) Byron Chiliquinga [ID], (1) and Alejandro Hallo [ID], (1)

(1) Internal Medicine, Eugenio Espejo Hospital, Quito, Ecuador

(2) Internal Medicine, NYU-Winthrop Hospital, New York, NY, USA

Correspondence should be addressed to Carlos Hallo;

Received 16 August 2019; Revised 1 October 2019; Accepted 22 October 2019; Published 13 November 2019

Academic Editor: Mehmet Soy

Caption: Figure 1: (a) Chest X-ray; AP view: bilateral, diffuse basal and perihilar alveolar infiltrate; (b) chest CT: bilateral effusion, increased vascularity, with bilateral infiltrates that converges to the posterior area.

Caption: Figure 2: (a) Chest X-ray; AP view: diffuse infiltrate redistributed to the bases; (b) chest CT: diffuse bilateral alveolar infiltrate.

Caption: Figure 3: Chest CT: bilateral alveolar infiltrates in a ground-glass pattern.
Table 1: Preliminary criteria for the classification of
catastrophic antiphospholipid syndrome (CAPS) [3].

(1) Evidence of involvement of three or more organs, systems,
  and/or tissues(a)
(2) Development of manifestations simultaneously or in less
  than one week
(3) Confirmation by histopathology of small vessel occlusion in
  at least one organ or tissue(b)
(4) Laboratory confirmation of the presence of anti-phospholipid
  antibodies (lupus anti-coagulant and/or anti-cardiolipin
Definite CAPS:
  (i) All four criteria
Probable CAPS
  (i) All four criteria, except for only two organs, systems,
    and/or tissues involved
  (ii) All four criteria, except for the absence of laboratory
    confirmation owing to the early death of a patient never tested
    for anti-phospholipid antibodies before the CAPS
  (iii) Criteria (1), (2), and (4)
  (iv) Criteria (1), (3), and (4) and the development of a third
  event between one week and one month after presentation, despite

Note: given that many times biopsy and histological confirmation of
small vessel occlusion cannot be obtained due to the critical
condition of the patients, a proposal has been made to substitute
the "histopathology criteria" by the exclusion of other diagnoses.
(a) Usually clinical evidence of vessel occlusions, confirmed by
imaging techniques when appropriate; renal involvement is defined
by a 50% rise in serum creatinine, severe systemic hypertension
(>180/100 mm Hg), and/or proteinuria (>500 mg/24h). (b) For
histopathological confirmation, significant evidence of thrombosis
must be present, although vasculitis may coexist occasionally. (c)
If the patient had not previously been diagnosed as having an APS,
the laboratory confirmation requires that the presence of
antiphospholipid antibodies must be detected on two or more
occasions at least 12 weeks apart (not necessarily at the time of
the event), according to the proposed preliminary criteria for the
classification of definite APS.

Table 2: Diagnostic workup in front of a patient with suspicion of
thrombotic microangiopathy (TMA) [3].

(1) To establish the suspicion of TMA
(1) Thrombocytopenia (<150 x 109/l or >25% of decrease)
(ii) Signs of microangiopathic hemolysis
(iii) Anemia ([+ or -] increase in mean corpuscular volume)
(iv) Reticulocyte count raised
(v) Lactate dehydrogenase (LDH) increased with haptoglobin
(vi) Direct Coomb's test negative
(vii) Blood smear searching schistocytes
(2) To look for organ involvement
(i) Neurological: confusion, headache, seizures, encephalopathy,
  and focal deficits
(ii) Renal: ARF, arterial hypertension, proteinuria, and hematuria
(iii) Cardiac: cardiac failure, hypotension, and ischemic
(iv) Pulmonary: ARDS and respiratory insufficiency
(v) Gastrointestinal: abdominal pain, intestinal angina, diarrhea,
  and vomiting
(vi) Hematological (thrombocytopenia): epistaxis, hemoptysis,
  menorrhagia, retinal hemorrhage, gastrointestinal bleeding, and
(3) To confirm organ involvement
(i) Blood analysis including renal function, cellular blood count,
  LDH, liver and pancreatic enzymes, creatin kinase, and troponin I
(ii) Renal biopsy: to confirm glomerular microthrombosis
(iii) CT/MRI brain: to determine neurological involvement
(iv) Electrocardiogram/echocardiogram: to document or monitor
  cardiac damage
(v) Chest radiograph/CT: to document lung involvement
(vi) Echography/CT: to document hepatic/pancreatic/intestinal
(vii) Fundoscopic examination: to document retinal vessel
(4) To investigate the etiology
(i) ADAMTS 13 activity: <5-10% (TTP)
(ii) If gastroenteritis (bloody diarrhea): Shiga toxin/STEC:
  positive (HUS)
(iii) If ADAMTS13 > 10%: secondary or associated TMA
(iv) Fundoscopic examination (malignant hypertension)
(v) Immunologic profile: ANA, ANCA, and aPL (autoimmune diseases)
(vi) Pregnancy test (pregnancy-related)
(vii) CT thoracoabdominal or PET: cancer-associated
(viii) Clinical history looking for drugs/heparin and anti-PF4
antibodies (HIT)
(ix) Complement studies: FH, FB, FI, anti-FH antibodies, and
  genetic study (aHUS)

(a) HUS: atypical HUS, ANA: anti-nuclear antibodies, ANCA: anti-
neutrophil cytoplasmic antibodies, aPL: anti-phospholipid
antibodies, CT: computed tomography, HIT: heparin-induced
thrombocytopenia; HUS: hemolytic uremic syndrome, PET: positron
emission tomography, STEC: Shiga toxin Escherichia coli, TTP:
thrombotic thrombocytopenic purpura.

Table 3: Comparison of characteristics of patients with
alveolar hemorrhage.

Case reports     Clinical        Physical exam       Chest
                presentation                         X-ray

Case 1           Decreased       Lung crackles      Diffuse
               visual acuity                        alveolar
               syncope cough                       infiltrate
Case 2         Alteration of     Lung crackles      Diffuse
                he state of                        alveolar
               consciousness                       infiltrate
Case 3           Hemoptysis      Lung crackles      Ground
                  dyspnea                            glass
Rangel et        Abdominal       Lung crackles      Patched
  al. [14]         pain                            opacities
                 Diarrhea                          in middle
                  Dyspnea                          and basal
Wan and         Asymptomatic        Venous         Opacities
  Tsang [18]                    thromboembolism
Isshiki et       Hemoptysis       Left lung         Diffuse
  al. [19]     Fever Dyspnea       crackles       infiltrates
                                                    in the
                                                   left lung
Martis et       Respiratory      Not reported     Not reported
  al. [15]        distress
Hambly et         Dyspnea        Not reported      Abnormal
  al. [16]       hemoptysis                       pattern not
Nguyen et         Dyspnea        Not reported        Small
  al. [17]       Productive                         patched
                   cough                           infiltrate

Case reports     Clinical               CT

Case 1           Decreased           No major
               visual acuity         changes
               syncope cough
Case 2         Alteration of        Ischemic
                he state of         areas in
               consciousness        the corpus
                   cough            callosum
                respiratory            and
                  distress           parietal
Case 3           Hemoptysis          Diffuse
                  dyspnea            alveolar
Rangel et        Abdominal           Ground
  al. [14]         pain               glass
                 Diarrhea       Hepatosplenomegaly
Wan and         Asymptomatic    Bilateral patched
  Tsang [18]                     consolidations
                                 and interlobular
                                septal thickening
Isshiki et       Hemoptysis       Ground glass
  al. [19]     Fever Dyspnea     pulmonary artery
                                thrombosis in the
                                 right basal lobe
Martis et       Respiratory        Not reported
  al. [15]        distress
Hambly et         Dyspnea          Ground glass
  al. [16]       hemoptysis
Nguyen et         Dyspnea          Infiltrate
  al. [17]       Productive      patched in the
                   cough        right middle lobe

Case reports     Clinical          Laboratory          Lupus
                presentation                        anticoagulant

Case 1           Decreased         Microcytic         Positive
               visual acuity        anemia,
               syncope cough    thrombocytopenia
Case 2         Alteration of      Pancytopenia          Not
                he state of                           requested
Case 3           Hemoptysis        Normocytic         Positive
                  dyspnea         normochromic
Rangel et        Abdominal       Abnormal liver       Positive
  al. [14]         pain             function
                 Diarrhea         Normochromic
                  Dyspnea          normocytic
                                 anemia High LDH
Wan and         Asymptomatic    Thrombocytopenia      Positive
  Tsang [18]
Isshiki et       Hemoptysis       Not reported        Positive
  al. [19]     Fever Dyspnea
Martis et       Respiratory      C4 complement        Positive
  al. [15]        distress          fraction
Hambly et         Dyspnea       Thrombocytopenia,       Not
  al. [16]       hemoptysis        lymphopenia        reported
Nguyen et         Dyspnea       Thrombocytopenia      Positive
  al. [17]       Productive

Case reports     Clinical         ANA        ANCA

Case 1           Decreased      Positive   Positive
               visual acuity
               syncope cough
Case 2         Alteration of    Positive   Negative
                he state of
Case 3           Hemoptysis     Positive   Negative
Rangel et        Abdominal      Positive   Negative
  al. [14]         pain
Wan and         Asymptomatic      Not        Not
  Tsang [18]                    reported   reported
Isshiki et       Hemoptysis     Negative   Negative
  al. [19]     Fever Dyspnea
Martis et       Respiratory       Not      Negative
  al. [15]        distress      reported
Hambly et         Dyspnea         Not      Negative
  al. [16]       hemoptysis     reported
Nguyen et         Dyspnea       Positive     Not
  al. [17]       Productive                reported

Table 4: Comparison of characteristics of patients with alveolar

Prothrombin      ACA IgM/IgG        Anti-         Heparin

Normal           IgM negative      Negative      Enoxaparin
               IgG 120 GPL/ ml
Normal          IgM negative       Negative      Enoxaparin
               IgG 100 GPL/ ml
Normal          IgM negative      No ordered     Enoxaparin
               IgG 155 GPL-U/ml
Normal           Not reported      Positive    Not initiated
Not reported      Positive         Negative    Discontinued
                 (unreported                      due to
                   values)                        surgery
Normal           Not reported      Negative     Not reported
Not reported       Positive        Positive    Discounted due
                                                to bleeding
Not reported       Positive        Positive     Not reported
Not reported       Negative        Positive     Not reported

Prothrombin      ACA IgM/IgG           Treatment

Normal           IgM negative      Prednisone 60 mg
               IgG 120 GPL/ ml    PO QD mycophenolate
Normal          IgM negative       Methylprednisolone
               IgG 100 GPL/ ml         1 gr IV QD
Normal          IgM negative      Methylprednisolone,
               IgG 155 GPL-U/ml     immunoglobulins
Normal           Not reported      Methylprednisolone
                                     1 g QD; fresh
                                     frozen plasma
                                      three units
Not reported      Positive          Anticoagulants,
                 (unreported          steroids, and
                   values)           plasmapheresis
Normal           Not reported      Methylprednisolone
                                        1 g QD;
                                  prednisone 25 mg QD
Not reported       Positive       Methylprednisolone
                                   1 g QD; rituximab
                                    375 mg/[m.sup.2]
Not reported       Positive          High doses of
Not reported       Negative              Oral

Prothrombin      ACA IgM/IgG         Evolution

Normal           IgM negative       Dyspnea of
               IgG 120 GPL/ ml    medium efforts
Normal          IgM negative           Died
               IgG 100 GPL/ ml
Normal          IgM negative         Clinical
               IgG 155 GPL-U/ml     improvement
Normal           Not reported        Clinical
Not reported      Positive          Infarction
                 (unreported        in a left
                   values)        pulmonary lobe
Normal           Not reported         Dyspnea
                                   recurrence and
Not reported       Positive          Clinical
Not reported       Positive            Image
Not reported       Negative         Hemoptysis
                                    and dyspnea

Prothrombin      ACA IgM/IgG       Bronchoalveolar     Bronchoscopy

Normal           IgM negative     Macrophages loaded   Not ordered
               IgG 120 GPL/ ml     with hemosiderin
Normal          IgM negative         Not ordered       Not ordered
               IgG 100 GPL/ ml
Normal          IgM negative         Not ordered       Not ordered
               IgG 155 GPL-U/ml
Normal           Not reported           Bloody           Friable
                                                        mucosa with
Not reported      Positive              Bloody           Diffuse
                 (unreported                            submucosal
                   values)                               bleeding
Normal           Not reported           Bloody         Not reported
Not reported       Positive          Not reported        Massive
Not reported       Positive          Macrophages       Not reported
                                      loaded with
Not reported       Negative             Bloody            Bloody
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Title Annotation:Case Report
Author:Loza, Grace; Hallo, Carlos; Chiliquinga, Byron; Hallo, Alejandro
Publication:Case Reports in Rheumatology
Article Type:Disease/Disorder overview
Date:Nov 30, 2019
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