Sandbox: Sima NourAli

Overview

[It is defined as a pleural fluid with hematocrit greater than 50% of the patient’s blood, although in cases of long standing haemothorax due to haemodilution, hematocrit level can be lower mimicking a hemorrhagic exudation. Therefore a hematocrit of 25-50% of the patients blood can raise the suspicion of haemothorax.PMID: 25922734] [Haemothorax refers to a collection of blood within the pleural cavity. By definition this bloody pleural effusion should contain a haematocrit value of at least 50% of the haematocrit of peripheral blood.PMID:20817498] [Hemothorax as a specific clinico-pathological entity can be defined in two ways. Morphologically, hemothorax is a pathologic accumulation of blood within the pleural cavity, between the lung surface and inner chest wall. From the clinical viewpoint, hemothorax is defined as the extraction of pleural fluid with a hematocrit ranging from at least 25–50% of peripheral blood [1]. It is important to realize that even hemothorax can appear as a hemorrhagic effusion with lower levels of hematocrit because there is a significant dilution in 3–4 days [1]. Moreover, levels of hematocrit in the blood need to be interpreted with knowledge of the phenomenon of postmortem hemolysis, especially with respect to the duration of the postmortem interval.PMID: 24529771]

Classification

[Spontaneous haemothorax (SH) is a subcategory of haemothorax.PMID: 25922734]

Pathophysiology

[Vascular Ehlers-Danlos syndrome (EDS IV) is a rare genetic disorder characterized by an alteration in the COL3A1 gene which encodes type III collagen. It is the most common type of collagen in vessels of medium size and certain organs such as the intestines and the uterus. The alteration of this type of collagen produces aneurisms and ruptures of vessels and organs. A high level of clinical suspicion is required for diagnosis. It is a complex disease whose management requires a multidisciplinary team to treat the different complications that may occur. We report the case of a 50-year-old man diagnosed with EDS IV detected incidentally after hemothorax secondary to a coughing spell.PMID: 29050841] [Fatal and non-fatal AVM-associated massive hemothorax is often linked to Osler–Weber–Rendu disease [25–30]. Osler–Weber–Rendu disease (hereditary hemorrhagic telangiectasia, HHT) is an autosomal dominant hereditary disease of blood vessel walls characterized by arteriovenous malformations of the multiple organs and telangiectases of the mucous membranes and dermis that result in tortuous, dilated vessels. HHT is marked by spontaneous recurrent epistaxis, multiple mucosal/skin telangiectases, visceral AVMs (lungs, liver, and brain), and family history./ EDS IV is rare, genetically based disorder of connective tissue, characterized by vascular dissection or rupture, intestinal perforation, or organ rupture/Additionally, there are other hereditary entities such as Loeys–Dietz syndrome, familial thoracic aortic aneurysm syndrome, or Shprintzen–Goldberg syndrome that predispose to aortic dissection/ PMID: 24529771] [Pathogenesis Bleeding into the pleural space can occur with virtually any disruption of the tissues of the chest wall and pleura or the intrathoracic structures. Blood that enters the pleural cavity is exposed to the motion of the diaphragm, lungs, and other intrathoracic structures. This results in some degree of defibrination of the blood so that incomplete clotting occurs. Within several hours of cessation of bleeding, lysis of existing clots by pleural enzymes begins. However, when this lysis is incomplete or bleeding is relatively large, clot formation is inevitably. Once the clot has been allowed to organize, it will adhere to the lung and pleura, making it difficult to remove. The agitation of cardiac and respiratory movement rapidly defibrinates the blood, and a fibrin clot thus formed is deposited on the visceral and parietal pleura, setting the stage for a trapped lung. In its early development, this thin membrane has little substance and is attached very loosely to the underlying pleural surface. By the seventh day, there is an angioblastic and fibroblastic proliferation. The membrane continues to thicken by progressive deposition and organization of the coagulum within the cavity. An understanding of the pathologic features of a clotted haemothorax makes it clear that, if possible, the clotted haemothorax should be evacuated within a reasonable time after onset of bleeding.PMID:20817498] [ Hsu et al. have proposed three mechanisms of bleeding in their SHP cases [44]. First, hemorrhage can result from a torn adhesion between the parietal and visceral pleurae. At autopsy, adhesions have been shown to be present in 50% of deceased >20 years of age who have had no history of pulmonary disease [44]. Second, bleeding can be caused by rupture of neovascularized bullae as a complication of subpleural emphysematous blebs [47]. Third, bleeding can result from torn congenital aberrant vessels branching from the cupola and distributed in and around the bulla in the apex of the lung [44,48]. Rupture of pleural adhesions spontaneously or after minor trauma causing massive hemothorax is a very uncommon event.PMID: 24529771]

Causes

[SHP is the most common cause of haemothorax.PMID: 25922734] [Previously reported malignancies causing spontaneous hemothroax include lymphangiosarcoma and vascular mediastinal schwannoma, lymphangioma, mediastinal teratoma metastatic choriocarcinoma, mediastinal or pulmonary malignancy, metastatic renal carcinoma, Abrikossoff tumor, pulmonary angiosarcoma, osterochondroma, Kaposiform endodermal sinus tumour, hemangioendothelioma, epithelioid hemangioendothelioma, hemangioma, hemangiopericytoma fibrous tumor of the pleura, hepatocarcinoma, periosteal chondroma, chondroblastoma of the rib, synovial sarcoma, osteosarcoma, Ewig sarcoma, neurofibrosarcoma, thymoma, mediastinal meningioma, thoracic neuroblastoma, pleural mesothelioma, chronic myeloid leukaemia.PMID: 21740393] [A spontaneous hemothorax is a rare clinical condition in the absence of trauma or iatrogenic causes (2). Hemothorax is defined as pleural fluid extraction with more than 50% of the concomitant hematocrit, and massive hemothorax is defined as the extraction of more than 1500 cc of blood upon chest drain insertion (1). It is a well-identified consequence of a blunt or penetrating chest trauma, intrathoracic vessel cannulation, chest drain insertion, thoracentesis, pleural biopsy, aortic aneurysm rupture, anticoagulation therapy, necrotizing lung infection, pulmonary infarcts, spontaneous pneumothorax, arteriovenous, malformation, endometriosis, exostoses, tuberculosis, uremia, hemophilia and diverse pleural malignancies (1,5). The most common malignancies associated with hemothorax comprise of schwanommas of von Recklinghausen disease, and soft tissue tumors (sarcoma, angiosarcoma, and hepatocellular carcinoma) (1). In the case of our patient, a possible cause for the sudden development of the hemothorax could have been the involvement of intercostal vascular structures by the tumor, or alternatively, given the vascularity of the tumor, its adhesions with the upper lobe of the left lung. This explanation is less likely since the bleeding from the tumor observed during thoracotomy was of mild character. PMID: 21740393] [ the complication of massive hemothorax in patients undergoing ECMO remains a medical challenge and is potentially life threatening because of the underlying problems of bleeding tendency,5 associated multiple organ failure, and the difficulty of performing the surgical techniques required for its treatment/PMID: 22726559] [spontaneous hemothorax Vascular disorders: rupture of thoracic aortic dissection/Arterial hypertension followed by atherosclerosis is the most important factor in developing aortic dissection. rupture of a saccular aortic aneurysm and traumatic rupture of the pericardial sac during cardiopulmonary resuscitation in individuals with hemopericardium. fatal spontaneous dissection of supra-aortic vessels without any evidence of aortic disease may occur, particularly during pregnancy and early puerperium. bronchial artery aneurysm rupture. neurysmatic internal thoracic artery, intercostal vessels, internal mammary artery aneurysm, or pulmonary congenital aberrant vessels. ruptured mycotic aneurysms.

innominate truncal dissection

Whayne and Spitz were confronted with a previously healthy heroin addict, who died suddenly of hemothorax due to rupture of a subclavian artery aneurysm [20]. He had been using his neck veins for mainlining. Toxicology can be very helpful when drug interaction or drug intoxication is a possible cause of spontaneous hemothorax.

pulmonary arteriovenous malformations (AVMs)

Fatal and non-fatal AVM-associated massive hemothorax is often linked to Osler–Weber–Rendu disease. very rarely associated with congenital heart disease:rupture of a patent ductus arteriosus/Eisenmenger syndrome, in which pulmonary infarction was complicated by life-threatening hemothorax and pneumothorax. Connective tissue disorders: Vascular Ehlers–Danlos syndrome (Ehlers–Danlos type IV, EDS IV) Marfan syndrome Loeys–Dietz syndrome familial thoracic aortic aneurysm syndrome Shprintzen–Goldberg syndrome Pleural disorders: spontaneous pneumothorax/Spontaneous pneumohemothorax (SPH) has been defined as the accumulation of >400 mL of blood in the pleural cavity in association with SP. Neoplasia: Spontaneous hemothorax is a rare, but well-documented complication of various neoplastic processes. The most common neoplasia-associated hemothorax involves neurofibromatosis type I (Morbus von Recklinghausen) and mesenchymal tissue neoplasias such as angiosarcomas, chondrosarcomas, and other soft-tissue tumors [50–70]. Malignant epithelial tumors can present as a hemothorax, particularly when they are metastatic to the intrathoracic area. There are several reported cases of hepatocellular carcinoma complicated by hemothorax [71–74]. Hemothorax as a rare but potentially fatal complication of extraordinarily rare tumor entities such as ectopic meningioma, germ cells tumors, or Abrikossoff's tumor has been discussed in several studies. Costal exostoses: Costal exostosis is another etiology for spontaneous hemothorax. These benign developmental abnormalities may exist singly or in multiple sites as autosomal dominant hereditary multiple costal exostoses. Exostosis or osteochondroma mainly occur in infants and children. We found several pediatric cases of spontaneous hemothorax secondary to solitary or multiple exostoses of the ribs [78–87]. Cheng et al. reported thorn-like costal osteochondroma presenting as hemothorax in an adult [88]. The pathophysiologic mechanisms proposed to explain the genesis of hemothorax involve trauma provoked by the exostosis: vascular wound directly caused by the tip of the exostosis on the pleura or the diaphragm [86,89]; spontaneous rupture of pleural dilated vessels because of chronic inflammatory process produced by longstanding friction of the exostosis on the pleura during breathing movements [89]. The shearing of the pleura or the diaphragm by the sharp-edged rib exostosis is potentially a fatal event [90]. This entity should be kept in mind as possible cause of spontaneous hemothorax in any decedents especially if no other explanation revealed by autopsy can be found. We strongly recommend careful examination of the inner surface of the thoracic cavity by palpation to reveal osteochondral irregularities. Gynecological disorders: Spontaneous hemothorax is a rare presenting symptom of intrathoracic endometriosis. Endometriosis is the presence of benign endometrial glands and stroma outside the uterus. Sites most frequently involved are the ovaries, uterine adnexa, and the pelvic peritoneum. Rarely, distant areas such as lungs, pleura, small bowel, kidneys, and bones are affected. Intrathoracic implantation of ectopic endometrial tissue presented with right-sided hemothorax is described in several case studies [91–93]. With regard to the implantation theory, several authors suggest that diaphragmatic fenestrations may be the route by which endometrial tissue gains access to the thoracic cavity. This theory also explains the pathogenesis of Meigs’ and pseudo-Meigs’ syndrome, in which patients are seen with ascites and right-sided pleural effusion [94,95]. This conception is consistent with the study of Vaughan et al. [96]. Other clinical presentations of thoracic endometriosis may include catamenial pneumothorax, followed by hemoptysis and pulmonary nodules. In cases of endometriosis, the findings usually include nonspecific hemosiderin-laden histiocytes, but rarely endometrial epitelial cells may be identified. An extremely uncommon source of hemorrhage has been described in association with extratubal ectopic pregnancy. Trophoblast was implanted on the diaphragm and subsequently penetrated into the pleura causing spontaneous hemothorax. Hematological disorders: In our review, several cases of spontaneous hemothorax were linked to hematological disorders such as hemophilia [98,99]. Hemophilia is an heritable disorder of blood clotting that results in delayed bleeding along with joint and muscle bleeding. Classic hemophilia is actually two distinct diseases resulting from mutations in the genes for factor VIII (hemophilia A) and factor IX (hemophilia B). While unexpected death due to hemorrhage remains a problem for individuals with hemophilia there has been change in the profile of cases with much longer survival and more complications related to human immunodeficiency virus and hepatis C from contaminated transfusions [100]. Many forensically relevant drugs such as sedatives, tranquilizers, anticonvulsants, and heparin are known to cause immune-mediated platelet destruction. Some studies in the literature reported anticoagulant-associated hemothorax, specifically, as a result of thrombembolic disease treatment [101–103]. In such cases toxicological evaluation may be desirable and highly recommended. Additional cases of hematology-related hemothorax include Glanzmann thrombasthenia, thrombotic thrombocytopenic purpura, and intrathoracic extramedullary hematopoiesis [104–107]. There have been several reports of patients presenting with intrathoracic extramedullary hematopoiesis due to a secondary process, such as myeloproliferative disorders, hemolytic anemia, hereditary spherocytosis, chronic asthma, and Gaucher disease [108,109]. Chute et al. reported the case of a 26-year-old male with a past medical history of beta thalassemia [110]. Fatal hemothorax was produced by spontaneous rupture of extramedullary hematopoietic pulmonary nodules. Miscellaneous: By reviewing selected articles, we identified studies reporting an association between spontaneous hemothorax and miscellaneous pathological entities. Hemothorax that has arisen from closed-chest cardiopulmonary resuscitation has been observed in several post-mortem studies [111–114]. Türk et al. reported spontaneous hemothorax secondary to a ruptured parasitic hydatid (Echinococcal) cyst of pulmonary parenchyma [115]. Moreover, when a hydatid cyst ruptures into a body cavity, the release of cyst contents can cause fatal allergic reactions [116]. Malaria is another rare parasitic etiology for spontaneous hemothorax and hemoperitoneum [117]. Alwitry et al. reported amyloidosis-induced spontaneous mediastinal hemorrhage with hemothorax due to perivascular and vascular wall involvement [118]. Amyloidosis is a disorder of protein metabolism, characterized by localized or systemic extracellular amyloid deposition. It may be primary in nature or reactive, and thus is secondary to a long-lasting chronic infection, inflammation, or malignancy. Yood et al. documented a series of 100 patients with amyloidosis [119]. They reported that in 41% of cases, the patients experienced one or more bleeding episodes, with fatal hemorrhage occurring in three cases. The staining properties and general appearance of amyloid are governed primarily by its compact and proteinaceous nature. The nature and organization of amyloid deposits allow it to be stained by routine Hematoxylin-eosin (amorphous, glassy material), Congo red (red-green birefringence when viewed under cross-polarized light), Thioflavin T or Alcian blue. However, immunohistochemistry is the best way to characterize amyloid [116]. A massive spontaneous unilateral hemothorax has also been observed in systemic lupus erythematosus (SLE) [120]. SLE is an autoimmune, multisystem, inflammatory disease that may involve almost any organ but characteristically affects skin, joints, serous membranes, and kidneys. Disorders of the respiratory system occur frequently, with clinical manifestations ranging from pleural disease to pneumonitis and interstitial fibrosis. Nevertheless, SLE-associated massive hemothorax is a quite uncommon pathologic entity.PMID: 24529771]

[Many blunt force injury cases, such as those that occur in vehicular collisions and following falls or jumps from heights, are often associated with fatal hemothorax.penetrating thoracic injuries produced by stab or gunshot wounds frequently lead to traumatic hemothorax/The wide range of pathologic processes that may trigger intrathoracic bleeding includes rupture of thoracic aortic dissection or aneurysm, spontaneous pneumothorax, pulmonary emboli, tuberculosis, various neoplasms, hematological abnormalities, connective tissue disorders, chest wall exostoses, and anticoagulants administration. Even infectious or parasitic diseases such as malaria or echinococcosis are capable of initiating non-traumatic bleeding into the chest cavity. In rare instances, ectopic pregnancy, pleural adhesion rupture, congenital heart defects, systemic diseases, extramedullary hematopoiesis or rare forms of malignancies may constitute the source of bleeding. Massive hemothorax is an infrequent, but potential life-threating complication of various iatrogenically-related procedures such as cardiopulmonary resuscitation, central vein catheterization, needle thoracocentesis, pleural or lung biopsies, and endoscopic thoracic interventions/PMID: 24529771] [Iatrogenous haemothoraces are known to occur as a complication of cardiopulmonary surgery, placement of subclavian- or jugular-catheters or lung- and pleural-biopsies/sclerotherapy of oesophageal varices, rupture of pulmonary arteries after placement of Schwann–Ganz catheters, thoracic sympathectomy and translumbar aortography./Spontaneous haemothoraces are generally caused by rupture of pleural adhesions (3–7% of all cases), neoplasma (schwanommas, soft tissue tumours, and hepatocellular carcinoma), pleural metastasis, and as a complication of anticoagulant therapy for pulmonary embolism.3 Less frequent causes reported in the literature are rupture of aneurysmatic thoracic arteries such as the aorta, mammarian arteries and intercostal arteries (e.g. Ehlers Danlos syndrome, and neurofibromatosis), rupture of pulmonary vascular malformations (Rendu-Osler-Weber syndrome), endometriosis, and exostoses.PMID:20817498] [Most cases of hemothorax are related to blunt trauma, procedures, neoplasm such as schwanommas of von-Recklinghausen disease and soft-tissue tumors, and vascular ruptures. Spontaneous pneumothorax is also a caused of spontaneous hemothorax. Hemothorax may result in respiratory distress, respiratory failure, retained clot, fibrothorax, empyema and extended hospitalization.PMID:26197910] [The primary cause of haemothorax is sharp or blunt trauma to the chest. Iatrogenous and spontaneous haemothoraces occur less frequently.PMID:20817498] [Coagulopathy: Drug related haemothorax Haemothorax may occur along with the administration of anticoagulant therapy. Blood can be collected in the pleural cavity either as a result of minimal trauma in the chest or spontaneous rupture of small vessels. Bleeding may also occur with the administration of systemic and intrapleural thrombolytics or in the setting of inherited coagulation disorders such as haemophilia (4,5). Haemothorax has been also reported in the setting of plasminogen activator user for venous thrombosis in patient with pneumonia. Glanzmann thromboastenia Glanzmann thromboastenia is an autosomal recessive disorder characterized by a lifelong bleeding tendency due to a quantitative and qualitative abnormalities of the platelet integrin αΠbβ3 [glycoprotein (GP) IIb; CD41/IIIa; CD61]. The GP IIb/IIIa is a receptor for fibrinogen, fibronectin, vitronectin, von Willebrand factor and thrombospondin, and mediates platelets aggregation via fibrinogen, firm adhesions and spreading. Common clinical manifestations include purpuric type skin bleeding, epistaxis, gingival bleeding and menorrhagia; haemarthrosis, haematuria, intracranial and visceral hemorrhage are rare but even rarer is SH (6,7). Bleeding could be controlled successfully by platelet transfusing before and after thoracentesis and tube replacement. It is usually self limited once coagulopathy is corrected. Hemophilia A Hemophilia A is a life-threatening hemorrhagic disorder caused by the development of an inhibitor against coagulation factor VIII (FVIII). Hemophilia is a X-linked hereditary disorder that consists of a defective and/or deficient FVIII molecule. It affects approximately 1 in 1 million inhabitants and can present as a sudden onset of serious bleeding in patients without a prior history of coagulation disorder (8). Hemophilia A manifests with early muscle and subcutaneous bleeding in 70% of cases. Haemothorax is a very rare event occurring in less than 1% of cases. Treatment of acquired hemophilia requires hemostasis to address hemorrhage and immunosuppressive therapy to suppress production of the FVIII inhibitor. Therapies that activate other coagulation system such as recombinant activated FVII or the active form of prothrombine complex concentrates derived from human plasma are effective (9). Evacuation of the residual haemothorax can be performed safely either with VATS or open thoracotomy.PMID: 25922734]

[Vascular: Haemothorax of vascular origin is often due to a rupture of the descending thoracic aorta, initially in the mediastinal and left pleural space due to the proximity of the pleural cavity. Rupture of the thoracic aorta in the right pleural cavity is rare. The ascending thoracic aorta bleeds mainly into the pericardium. Aortic dissection and aneurysm affect patients with risk factors such as hypertension, congenital aortic anomalies (aortic coarctation, bicuspid aortic valve disease). The treatment and the course depend mainly on the severity of the initial clinical manifestation, the type and extent of aortic lesion and the patient history. Radiological investigation are the key for diagnosis: chest X-rays show mediastinal enlargement and pleural effusion. CT scan with contrast is the tool of choice for the diagnosis and the management of patient with suspected haemothorax caused by aneurysm or aortic dissection. For aneurysm, surgery is indicated when patient become symptomatic. In the absence of surgery, radio-clinical strict monitoring is necessary. Dissections of the ascending aorta (Stanford type A) must be operated in an emergency, while decision for surgery of descending aortic dissection (Stanford type B) is made on assessing the case of acute complications. Thoracic drainage in these situations is not recommended because it can lead to hemodynamic instability. Ehlers-Danlos syndrome (EDS) EDS forms part of a spectrum of inherited connective tissue disorders that includes osteogenesis imperfecta and has an incidence of 1 in 5,000. It is an inherited disorder of collagen synthesis and is characterized by hyperlaxity of joints. There is also a tendency to bruising and bleeding which is a feature of the vascular type IV EDS. There are six variants of EDS of which type III (joint hypermobility syndrome) is the most frequent. Type IV is an autosomal dominant variant, known as vascular EDS and is rare, accounting for ~10% of the EDS variants. The underlying genetic mutation is that of COL3A1 gene, resulting in abnormalities in type III procollagen production and synthesis (10). Respiratory manifestations of vascular EDS although not always common, have been described and include recurrent hemoptysis, bullae and bleb formation, and spontaneous hemo-pneumothoraces. Most frequent initial manifestations of vascular EDS is arterial dissection or colon rupture. Management of patient with vascular EDS is difficult because there is no specific treatment. Vascular complications are general sudden and catastrophic and gradual vascular dilatation such as seen in Marfan’s syndrome is not a feature in EDS. Patients with hemodynamic instability and rapid rate of bleeding should be managed with surgery performed with open approach. Von recklinghausen disease (VRD) Type I neurofibromatosis (NF-1) or VRD is known to cause SH. It is an autosomal dominant disease with an occurrence rate of 1 in 3,000 (11). Its prevalence is similar in all races and sexes, and is usually diagnosed in adulthood, since its clinical characteristics develop throughout life. This entity can affect any organ system, especially connective, nervous and vascular tissues, and is characterized by skin tumors and abnormal cutaneous pigmentation. Two main pathogenetic mechanism have been advocated for vasculopathy associated with VRD: (I) direct vascular invasion from adjacent tumors such as schwannoma, neurofibroma, or neurofibrosarcoma (12); and (II) vascular dysplasia with thickening and concomitant reduced strength of the vessel wall and aneurysm formation (13). Invasive tissue leads to compression of the vasa vasorum with subsequent ischemia and weakness of blood vessels. Small vessel damage is due to dysplasia of the wall due to proliferation of the intimae and muscolaris, loss of the media and fibrosis of the adventitia. This initiates a stenosis of the vessel wall, potentiating vessel wall weakness and friability with subsequent risk of rupture.Vascular dysplasia often causes thickening and concomitant reduced strength of the vessel wall leading to aneurysm formation. Treatment options are dependent on the patient’s hemodynamic stability. Endovascular embolization is indicated if there is hemodynamic stability. As an alternative, thoracotomy with surgical ligation is indicated in cases of active bleeding, with associated hemodynamic compromise. Regarding the prognosis of NF-1 in patients with haemothorax, the disease mortality is 36% and postoperative mortality is 33%. Recently published cases suggest that coil embolization offers the best results (11). Go to: Rendu-Osler-Weber syndrome Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant hemorrhagic disorder characterized by multiple cutaneous, systemic, and/or pulmonary arteriovenous malformations (AVMs). Almost invariably, the patients have epistaxis, but bleeding may occur from any AVM site. Bleeding from pulmonary lesions usually occur as haemoptysis and rarely as SH. Only a few fatal cases of such rare presentation of this syndrome have been reported (14). The pulmonary complications of Rendu-Osler-Weber syndrome were first recognized in 1917, 20 years after the first report of pulmonary AVM. For unknown reasons, pulmonary AVMs, which may be congenital or acquired, are more common on the left side and occur most commonly in the left lower lobe. Through these vessels, blood is shunted (usually from branches of the pulmonary artery) into the pulmonary veins. Rupture of an AVM may occur at any age and is not absolutely dependent on the size of the lesion. Rupture and other combination are more common in women. About 15% of patients with Rendu-Osler-Weber syndrome have pulmonary arteriovenous fistulas, and intrabronchial rupture, has been reported in 8% to 25%. Intrapleural rupture with consequent haemothorax is a less common and potentially fatal combination. Once pulmonary AVM has bled, it should be treated aggressively with either surgical resection or embolization as soon as possible to prevent life threatening rupture of the lesion. Until the late 1970s, the treatment of choice for pulmonary AVM was surgical resection or ligation of the arteriovenous fistula. When emergency local excision or segmental resection of the lesion could not be performed due to precarious health conditions or the occurrence of multiple lesions, lobectomy or pneumectomy represents a salvage option. Nowadays, embolotherapy appears to be the preferred treatment modality, since it preserves lung function and minimizes morbidity associated with thoracotomy or lung resection.PMID: 25922734] [Neoplasia Angiosarcoma Angiosarcoma is a rare malignant vascular tumor that accounts for <2% of al sarcomas. It usually occurs in middle aged patients, and the most common locations of the primary tumor are the skin, heart, liver, spleen, bone and GI tract. Symptoms are closely related to tumor location. The most common metastatic site for angiosarcoma is the lung. Its development can be rapid. Since the pleural effusion is directly related to pleural invasion, it usually has a bloody appearance with high hematocrit value also containing neoplastic cells. Schwannoma Schwannoma is a neurogenic tumor arising from the Schwann cells of the neural sheath. It originates commonly in the extremities, head and neck. Most intrathoracic neurogenic tumors originate in the posterior mediastinum, with 5.4% arising in the thoracic wall (16,17). Benign schwannomas rarely manifest as a pleural effusion. It is often impossible to establish whether these tumors are benign or malignant before surgery, but the risk of malignancy for this kind of tumour is very small (2-5%). If the patient has VRD (discussed above) or a history of radiation exposure, the risk of malignancy increases to 10-20%. Magnetic resonance represent a very useful tool to obtain a complete diagnosis. Thymoma Thymomas represent a rare cause of SH (18). The cause of spontaneous rupture of a thymoma is obscure. An enlargement of a thymoma may cause rupture and subsequently produce haemomediastinum or haemothorax. In cases of malignant thymoma, rupture may be attributable partly due to tumour invasion to adjacent vital structures. Another mechanism could be spontaneous intratumor hemorrhage without enlargement. VATS surgery has not been accepted completely for thymectomy. As thymomas have a potential malignant behaviour, tumor resection accompanied by total thymectomy is recommended. In addition, tumor dissection from adjacent structures is required. Hepatocarcinoma Spontaneous rupture of hepatocellular carcinoma (HCC) is known to be a condition with poor prognosis. The liver is an organ inside the peritoneal cavity, so the rupture of HCC generally causes haemoperitoneum. Among these cases, few reports exist on the rupture of HCC originating from the caudate lobe in which a haematoma is often formed in the omental bursa (also known as the lesser sac). On the other hand, haemothorax is a very unusual presentation of ruptured HCC and is accompanied by a high mortality rate secondary to uncontrollable haemorrhage. This is due to the negative pressure inside the pleural cavity that makes spontaneous haemostasis difficult (19). The diaphragm is a muscular tissue which separates the thoracic cavity from the abdominal cavity and has three openings: a caval opening, an oesophageal hiatus, and an aortic hiatus. Since the caudate lobe is a section that anatomically comes in contact with the inferior vena cava, HCC and related haematoma could intensely retract the inferior vena cava. Consequently, it is possible that the blood is flowing along the connective tissue sheaths of the inferior vena cava, and, after entering the mediastinum through the caval opening, may ruptures the pleura and flows into the right pleural cavity causing haemothorax.PMID: 25922734] [Miscellaneous: Costal exostoses Exostosis occurs in the ribs either sporadically or as a manifestation of a genetic disorder known as hereditary multiple exostoses (HME). HME is an autosomal-dominant condition characterised by exostoses that can appear in different skeletal structures. Lesions mainly occur in infants and children, and usually cease enlarging in puberty. HME in the ribs is rare and generally asymptomatic, and approximately 30 cases of intrathoracic complications have been reported. These complications include haemothorax, pneumothorax, diaphragmatic or pericardial lacerations and visceral pleural injury (20). The exact mechanism of bleeding is not completely clear. It may be due to injury to the visceral pleura and underlying pulmonary parenchyma from direct contact with the sharp exostoses; bleeding may also result from rupture of dilated vessels associated with long term friction between the intrathoracic exostoses and visceral pleura, which also cause pneumothorax. The respiratory motion of the lower lobe is greater than that of the right middle or upper lobes. Thus, pneumothorax may easily occur in both the lower lobe and visceral pleura as a result of lung injury caused by exostoses (21). Surgical approach with either VATS or thoracotomy is needed to resect the exostoses and prevent recurrence. Extralobar pulmonary sequestration (EPS) EPS is an embryonic anomaly. It is considered to be an accessory lobe and was first describe in 1861 by Rokitansky and Rektorik. EPS, an entity in which an abnormal lung segment is enclosed within its own pleural membrane, is completely separated from the tracheobronchial tree and accounts for 25% of all pulmonary sequestrations (22,23). The location, usually related to the left hemidiaphragm, may vary between the lower lobe and the diaphragm within the mediastinum, the lung, pleural and pericardial space or the retroperitoneum. Symptoms are usually ipsilateral chest pain and respiratory failure with sudden onset caused by haemothorax or infarction. Extramedullary haematopoiesis (EMH) EMH is a common compensatory mechanism for chronic anaemia, found in patients with haemoglobinopathies such as thalassaemia, sickle cell disease and hereditary spherocytosis (24). These patients are usually asymptomatic. EMH usually manifests in the thorax as multiple posterior mediastinal, paravertebral masses or masses along the lateral margins of the ribs. B-thalassemia remains the most common cause of EMH, these patients are under a constant hypoxia due to decreased blood oxygen load and defective haemoglobin unload in the periphery. The constant and long lasting hypoxia leads to enhanced rate of erythropoiesis and increased intestinal iron absorption. The former imply a marked bone marrow hyperplasia and extramedullary foci of haematopoiesis, resulting in spleen and liver enlargement or even tumor-like masses in several sites, mainly paravertebral (25). These masses frequently remain asymptomatic but in certain patients may cause different syndromes due to compression of the surrounding structures. The extramedullary foci consist of haemopoietic cells and adipose elements. They are not circumscribed by a capsule. The mass is extremely vascular and contains little fibrous tissue. The structure renders the mass prone to haemorrhage. All the published cases of extramedullary foci bleeding deal with the pleural cavity; the reason is not clear but it may be related to preferential localisation or specific tissue structures rendering them vulnerable to rupture due to thoracic respiratory movements (26). Endometriosis SH may result from endometrial implants on the pleural surface and then response to cyclical hormonal changes in menstruating women. Endometrial implantation occurs as a result of migration of endometrial tissue through fenestrations on the diaphragm. This phenomenon is known as catamenial haemothorax. This entity is usually managed by hormonal therapy designed to limit oestrogen or produce amenorrhoea (27). In case of failure of hormonal therapy, exploration of the pleural space and resection of endometrial implants may be necessary. Bilateral spontaneous haemothorax (SH) Bilateral SH represents a very rare entity with only eight cases described in the literature over the last fifty years. A total of 50% of them were related to cardiac angiosarcoma (28). The others were related to subclavian artery aneurysm, endometriosis and iatrogenic coagulopathy. The eighth case was idiopathic. Thus primary or metastatic pleural angiosarcoma should be considered as the main cause of spontaneous bilateral haemothorax.PMID: 25922734]

Natural History, Complications and Prognosis

[Chronic and retained hemothorax can lead to empyema, chronic fibrothorax, or lung entrapment with impaired pulmonary function.PMID: 24529771] [Despite well-studied oncogenesis and treatment modalities, the prognosis for all malignancy-related hemothorax remains poor.PMID: 24529771] [Authors report on their experiences with the treatment of thoracic empyema developing from the suppuration of haematoma following thoracic injury. In 30 of 82 patients suppuration of the thoracic cavity has developed. 6 of the 30 patients with empyema were treated first in our Department all 6 healed on drainage whereas in 24 patients, admitted from other departments, the following measures were necessary: 2 pleura lavages under the control of thoracoscope, 3 early decortications, 14 decortications, 5 lung resections and decortications with a decrease of the respiratory surface. Attention is called to the necessity of early and adequate treatment which is a prevention of complication (suppuration). Light is given to the factors which most frequently promote suppuration of the thoracic cavity, developing from traumatic haemothorax. Attention is called to secure the necessary personal and material conditions to the preventive treatment.PMID: 1681146] [Residual clot may organize and fibrose, resulting in a loss of lung volume and empyema if untreated./RH can be a source of significant morbidity if complicated by pleural sepsis or lung entrapment [2–6,14]. Residual/retained haemothorax therefore should be detected and treated early to prevent these complications. /PMID: 25813733]

Diagnosis

[In the presence of bloody effusion the first step is to check the haematocrit to confirm a haemothorax identified, as stated above, between 25% to 50%. It is important to consider that an haemothorax can appear like a haemorrhagic effusion with a lower hematocrit due to significant dilution in 3-4 days. Also an enhanced CT of the chest can provide helpful information about the etiology. For the neoplastic etiologies, cytology of the pleural fluid is useful, but immunochemical markers may increase the yield and degree of confidence. For the endometriosis cases, findings also include haemosiderin, histiocytes but rarely endometrial epithelial cells.PMID: 25922734]

Symptoms

[The clinical presentation is variable and includes a rapid progression of symptoms of chest pain and dyspnea that can be life threatening when hemodynamic instability and hypovolemic shock occurs.PMID: 25922734] [Non-traumatic acute intrathoracic hemorrhage can occur at any age, usually heralded by the onset of severe chest pain and dyspnea.PMID: 24529771]

Imaging Findings

[detection of this complication via chest radiography is not possible unless the volume of hemothorax exceeds 175 milliliters.PMID: 27299139]

Treatment

[Treatment of SHP includes, in addition to fluid resuscitation and blood transfusion, tube thoracostomy for drainage of the haemothorax and re-expansion of the lung. Following chest drain insertion patients can be potential candidates for surgery via either video-assisted thoracoscopic surgery (VATS) or open thoracotomy.PMID: 25922734] [Regardless of causes, any massive haemothorax requires attention for fluid resuscitation and blood transfusion. All patients should be promptly resuscitated according to ATLS guideline by setting up two large bore branulas and fluid resuscitated accordingly. A chest tube should be inserted under with a sterile technique to evacuate the haemothorax. Drainage should be assessed hourly and decision for surgical intervention should be made if any one of the following conditions is fulfilled: 1. Evacuated more than 1000cc after initial chest tube insertion 2. Persistent drainage about 150cc-200cc hourly for 3 to 4 hours 3. Repeated blood transfusion in view of hemodynamically instability.PMID: 25638240]

[The successful management of hemothorax depends on many factors, namely the severity of the blood loss and subsequent hemodynamic stability of the patient.PMID: 21740393] [Video assisted thoracic surgery (VATS) has been shown to be highly successful for treatment of these residual collections, especially when used early [3]. Intra-pleural streptokinase instillation (IPSI) has been advocated as an alternative in low-resource settings where the relatively costly and sophisticated technique of VATS may not be available, feasible or applicable./simple interventions in the form of oxygen therapy and ICD placement significantly reduce the morbidity and mortality /PMID: 25813733] [Initial treatment Chest tube drainage In most cases, chest tube drainage by means of a large calibre (≥28 French) tube is an adequate initial approach unless an aortic dissection or rupture is suspected.2, 3 After the tube thoracostomy is performed, a chest radiograph should always be repeated in order to identify the position of the chest tube, to reveal other intrathoracic pathology and to confirm whether the collection of blood within the pleural cavity has been fully drained. Surgical approach in the acute phase

The criteria for surgical exploration, as detailed in the literature, are blood loss by chest tube 1.500 ml in 24 h or 200 ml per hour during several successive hours and the need for repeated blood transfusions to maintain haemodynamic stability.4, 5, 6

Patients with active blood loss but with stable haemodynamics can be treated with Video-Assisted Thoracoscopic Surgery (VATS), not only to stop the bleeding but also to evacuate blood clots and breakdown adhesions. A series of 50 VATS procedures, performed in patients with traumatic haemothorax, demonstrated active blood loss in eleven subjects.4

Thoracotomy is the procedure of choice for patients with haemodynamic instability due to active bleeding.2 Surgical exploration allows control of the source of bleeding and evacuation of the intrathoracic blood. Prophylactic antibiotics

Antibiotic treatment following haemothorax reduces the rate of infectious complications.7, 8, 9, 10 The Eastern Association for Trauma developed guidelines based on nine prospective placebo-controlled studies, including several double blinded studies and two meta analyses. Most of the cases enrolled in these studies were penetrating chest traumas, but some studies also included patients with spontaneous haemothorax. The guidelines recommend the use of first generation cephalosporins during the first 24 h in patients treated with chest tube drainage for haemothorax. In the included studies however, a broad range of antibiotics was applied. When empyema occurs during chest tube drainage, antibiotic treatment should be directed to Staphylococcus aureus and Streptococcus species.8

In a comment on this guideline, results of different studies were combined to generate incidence rates. The authors concluded that prophylactic use of antibiotics during at least 24 h after the start of chest tube drainage for haemothorax, reduced the incidence of pneumonia from 14.8% to 4.1%.9 The incidence of empyema decreased from 8.7% to 0.8%.

Another randomised controlled study, performed after the publication of these guidelines, also revealed fewer infectious complications in the group of patients treated with prophylactic antibiotics.10

The duration of antibiotic treatment remains a point of discussion and recommendations vary from 24 h to the moment of chest tube removal. In general, 24 h of antibiotic treatment is advised in traumatic haemothorax.8 Whether antibiotic prophylaxis is useful for spontaneous haemothorax has not been investigated accurately. Intrapleural fibrinolytic therapy

Intrapleural fibrinolytic therapy (IPFT) can be applied in an attempt to evacuate residual blood clots and breakdown adhesions when initial tube thoracostomy drainage is inadequate. Retention of blood in the pleural cavity may lead to lung entrapment, chronic fibrothorax, impaired lung function and infection. Several small non-randomised studies report on IPFT with streptokinase (250,000 IU), urokinase (100,000 IU or 250,000 IU) or tissue plasminogen activator (TPA).11, 12, 13, 14, 15, 16 The intervals between the day of onset of haemothorax and the start of treatment varied from 4 to 165 days. Whether IPFT can be initiated prior to the fourth day is not clear from the published reports. Generally, it is advised to evacuate the clotted haemothorax within 7–10 days.4

Reports on duration of treatment with IPFT vary between 2 and 9 days for streptokinase and 2–15 days for urokinase.

In most cases, treatment with IPFT leads to complete resolution of radiographic abnormalities, through evacuation of blood clots and loculated effusions. Less than 10% of cases need a more aggressive treatment by means of surgical decortication.

Bleeding complications due to a possible systemic effect of fibrinolytic substances were not reported in the studies using streptokinase and urokinase. A study using recombinant tissue plasminogen activator as a fibrinolytic agent, was reported on one patient who developed haematuria requiring blood transfusion.16

The relationship between the time frame of IPFT or conversion to surgical intervention and the risk of developing long-term complications has not been established in the published literature.

If chest tube drainage and IPFT does not lead to sufficient resolution of the retained clots, surgical intervention should be considered. Surgical approach in a later phase VATS

Optimal evacuation of residual clots, breakdown of adhesions and loculated effusions is important in order to prevent a complicated course leading to empyema or fibrothorax. A volume of 500 ml of blood or an amount of blood filling one third of a hemithorax is considered an indication for surgery.17, 18, 19, 20

Chest X-ray seems to be an inadequate tool in establishing the indication for VATS. The surgical procedure should therefore be preceded by computer tomography (CT), to be able to detect locations and residual clots with high accuracy.18, 21, 22

The estimated amount of fluid on CT scans has been shown to correlate very well with the true amount of fluid harvested by VATS.22

VATS evacuation of the haemothorax or retained clot can be performed safely. One-lung ventilation is not required. A single lumen tube can be used with directions to anaesthesiologist to decrease tidal volume or intermittently hold ventilation during the procedure. If cardiac, great vessel, or tracheobronchial injury is found, conversion to thoracotomy can be performed expeditiously.

A randomised study in patients with incomplete resolution of clots and blood after chest tube drainage reported shorter length of hospital stay and shorter duration of tube drainage in a group of patients treated with VATS as compared to a group treated with additional tube drainage.17

Several prospective and retrospective non-randomised studies in small groups of patients show favourable results of VATS (80%–100%) with high effectiveness and low morbidity.6, 19, 21, 20, 21, 22, 23, 24, 25, 26

However, the methods of evaluation were not reported in all of these studies and IPFT was not integrated in the therapeutic strategy. An optimal period between trauma and VATS of 48–72 h is repeatedly advocated, although a longer interval is more common.6, 19, 21, 26

Longer intervals between the start of haemothorax and VATS lead to increased rates of complications, according to some authors.19, 20 Thoracotomy

Thoracotomy is the procedure of choice for surgical exploration of the chest when massive haemothorax or persistent bleeding is present. At the time of surgical exploration, the source of bleeding can be controlled and a haemothorax evacuated. Thoracotomy is usually required for adequate empyema drainage and/or decortication. In 10% of cases a thoracotomy is necessary to treat the haemothorax.6

A longer time span between the appearance of haemothorax and VATS increases the chance of intraoperative conversion to thoracotomy, prolongs postoperative drainage time and is associated with a higher incidence of hospital admissions.19, 27 When haemothorax is complicated by empyema, the duration of hospital stay also increases.PMID:20817498] [The management is related to the patient stability (Figure 1). Thoracoscopic draining is usually for stable patients. In haemodynamically unstable patients or if the rate of bleeding is more than 500 mL/hr in the first hour with 200-300 mL/hr subsequently, early surgical approach is favoured. Correction of coagulopathy is mandatory in every case of anticoagulant induced bleeding. Embolisation remains a valid option in the treatment of vascular abnormalities. The management of the residual haemothorax is controversial with a growing number favouring early VATS particularly if a significant amount of clot is present to prevent fibrothorax and restrictive physiology.PMID: 25922734]

Surgery

[In haemodynamically unstable patients inspection and drainage of the pleural cavity by thoracotomy is indicated, whereas in haemodynamically stable patients VATS is considered the treatment of choice.PMID:20817498] [The management of hemothorax has been a complex problem since it was 1st described over 200 years ago.PMID:26197910] [Traditionally, lrage hemothorax is treated primarily by closed thoracic drainage by inserting a large-caliber chest tube in stable patients/In hemodynamically unstable patients with more than 1,000 ml of blood drainage from the initial thoracotomy or ongoing blood losses of more than 100 to 200 ml/h, an early surgical approach with ongoing resuscitation is needed./Video-assisted thoracoscopic surgery （VATS）, minimally invasive surgery, grows and finds new applications for the patients with hemothorax as both diagnostic and therapeutic interventions/VATS is an accurate, safe, and reliable operative therapy in the 5-day post event window, but there is a decreasing success rate after this time period.PMID:26197910] [*chest tube drainage

• Video-assisted thoracoscopy PMID:9262119]