9. BLEEDING 1. Introduction The importance of gross and occult bleeding and their influence on organism.

Gross bleeding is connected with damage of larger artery or vein, either traumatic or in pathologically changed tissue (tumour, ulcer). Gross blood loss leads to haemorrhagic shock, lesser bleeding presents as acute anaemic syndrome. In patients with coagulopathy these symptoms are more pronounced, last longer and are more dangerous even in case of minor bleeding (tooth extraction). For treatment, it is necessary to discover the source of bleeding. The source is either visible (arterial bleeding in limb trauma etc.) or invisible (urogenital tract, gastrointestinal tract). In that case it is necessary to visualise the source of bleeding, either radiologically or endoscopically. It is also necessary to evaluate the amount of blood loss and eventual organic damage (acute liver failure after oesophageal bleeding in cirrhosis, cerebral coma after intracranial bleeding). Treatments consists of treatment of shock and cessation of bleeding. Shock is treated by volume replacement, either with full blood or crystalloids, in case of thrombopathy or coagulopathy, also the replacement of missing factor(s) is needed (platelets, plasma proteins). In some cases the bleeding stops spontaneously (haematuria) or after transfusion (bleeding from peptic ulcer), in other cases an instrumental (nose tamponade) or endoscopical treatment (local injection of vasoconstriction agents) is needed. Chronic small blood loss can be either visible (haematuria, metrorrhagia, enterorrhagia), or occult. In later case the source is usually in gastrointestinal tract (tumour, ulcer) and it needs to be evaluated. Chronic blood loss leads to hypochromic anaemia, either clinically silent or with anaemic symptoms (vertigo, dispnoea, angina). 2. Pathology and pathophysiology of bleeding 2.1. Anatomy and function of blood vessels under normal conditions. Anatomical localisation of pathological process can predispose certain vessels to bleeding (i.e. in haemorrhagic stroke the site of bleeding is frequently to

internal capsule). Also anatomy of vessel can be responsible, mainly if the vessel wall is pathologically changed (atherosclerosis, vasculitis, collagenoses). Abnormal anatomy of vessel wall can predispose to bleeding in patients with vascular purpuras, but it is often difficult to prove the vessel damage on clinical grounds. 2.2. Mechanism of blood clotting Three factors are needed for normal haemostasis: vessel wall, platelets and plasma proteins (coagulation factors). Primary haemostasis occurs in seconds, as platelet plug is formed. There are four steps of primary haemostasis: platelet activation, adhesion, degranulation and aggregation. Arachidonic acid plays an important role, as it is converted by cyclooxygenase either to thromboxan A2 (which occurs in platelets and promotes their activation) or to prostacyclin PGI1 (this occurs in endothelial cells and have an opposite effect). Secondary haemostasis last minutes. During secondary haemostasis, coagulation factors of internal and external cascade are activated and fibrin is formed from fibrinogen. It is important to notice that internal and external coagulation cascade are interconnected - factor VIIa activates not only X, but also IX to IX a, making the internal pathway of physiological importance. 2.3. The mechanism of bleeding in healthy person. Most of the bleeding episodes in healthy people are traumatic. In most cases of non-traumatic bleeding there is an inherited or acquired abnormality of vessel wall (arteriovenous malformation, aneurysma, peptic ulcer). The bleeding ceases with reconstitution of vessel wall integrity, because the platelets and coagulation factors function normally. 2.4. Mechanism of bleeding in people with bleeding disorders. 2.4.1. In defects of primary haemostasis, the bleeding becomes immediately after trauma or surgical procedure. It answers to local measures (compression, immobilisation). In severe cases, however, the platelet transfusion is necessary.

2.4.2. In defects of secondary haemostasis, bleeding occurs hours or days after trauma or surgical procedure. Spontaneous bleeding can also occur, especially to joints, soft tissues or genitourinary tract. The treatment consists of replacement of missing coagulation factor(s). 3. Clinical manifestation of bleeding 3.1. Epistaxis. Usually is caused by vascular malformation, hypertension, drugs, tumour or trauma in nasopharyngeal localisation. Diagnosis is made by aspection, instrumental aspection, visualisation of paranasal sinuses endoscopically or by X-ray. Therapy is usually local - nose tamponade, rarely the operation is needed. 3.2. Eye bleeding. It is not usually life-threatening, but can lead to damage of vision, if localised in certain areas (i.e. retinal or vitreous bleeding), while in other cases is not significant, just frightening (subconjunctival bleeding). 3.3. Ear bleeding. Can be a sign of tumour or inflammation, but often comes in fractures of skull basis and can be associated with intracerebral bleeding. X-ray and in appropriate cases also CT scan has to be made. 3.4. Bleeding after dental extraction - if severe, can lead to discovery of previously silent coagulation defect. Local and non-specific antifibrinolytic treatment (e-aminocaproic acid) is usually appropriate. 3.5. Other bleeding in ORL localisation can lead to airway obstruction and/or risk of suffocation. 3.6. Haemoptysis, haemoptoe - comes in coagulation abnormalities, pneumonia, lung cancer, tuberculosis, mycosis, mitral valve stenosis, cardiac decompensation or aspiration of foreign body. Diagnostic procedures and treatment should generally be conservative (chest X-ray, CT, bronchoscopy, bronchial arteriography). Bronchoscopic evacuation of blood can be helpful. In most cases, the pulmonary bleeding is not life-threatening and stops spontaneously. In rare situations

when gross bleeding occurs, either surgical treatment or artificial embolisation of bleeding bronchial artery is needed). 3.7. Gastrointestinal bleeding is caused by drugs (usually aspirin-containing or NSAIDs), peptic ulcer or oesophageal varices. It manifests as haematemesis, melaena or enterorrhagia. Endoscopical diagnosis is a method of choice in most cases and should be performed as soon as possible, because endoscopical therapy (sclerotization of varices, adrenaline injection in peptic ulcer bleeding, laser photocoagulation) can often be instituted. Angiography is helpful only during active bleeding (not after it cessation). In liver disease, haemocoagulation abnormalities are often present, which can be corrected by fresh frozen plasma. In gross or refractory bleeding, surgical treatment after volume repletion is necessary. Mortality of gastrointestinal bleeding still approaches 10%. 3.8. Haematuria (microscopical or macroscopical) usually is not lifethreatening nor does it lead to iron-deficiency anaemia, because usually it does not escape early detection. However, it can be a presenting symptom of serious disorder (trauma, urolithiasis, tumour, infection, glomerulonefritis) and the cause of bleeding can be sought. Both visualisation (urography, ultrasound CT, endoscopy) and function methods should be employed according to the clinical situation. In some cases, endoscopical or ultrasound methods can be utilised also for treatment of urolithiasis or bladder papilloma. 3.9. Metrorrhagia can be life-threatening. Usually the cause of bleeding is gynaecological (myomatosis, cancer, hormonal dysbalance), but it can be a presenting sign of rare hereditary (factor V deficiency, dysfibrinogenaemia) or acquired (idiopathic thrombocytopenic purpura, disseminated intravascular coagulation) bleeding disorder. 3.10. Intraperitoneal bleeding is either traumatic or becomes as a part of splenic or hepatic disorders (sepsis, infectious mononucleosis, myelofibrosis, malaria, liver haemangioma). If shock together with lower abdominal symptoms occur, gynaecological cause should be sought (ectopic pregnancy). Treatment is surgical - splenectomy, suture or partial liver resection, salpingectomy.

3.11. Skin and mucosal membrane haemorrhage usually points out to bleeding disorder. Teleangiectasia can be hereditary (Rendu-Osler-Weber disease) or acquired (liver disease, pregnancy, flebectasia). Purpura senilis, Cushing disease or renal failure can lead to skin haemorrhages caused by collagen depletion of vessel walls. They can be presenting sign of acquired platelet disorder (ITP), leukaemia, anticoagulation overdose or disseminated intravascular coagulation. Cutaneous purpura fits into a picture of a number of infectious disorders (meningococcaemia, sepsis, leptospirosis, Rocky mountain fever), autoimmune diseases (vasculitis) or skin disorders. 3.12 3.13 Contagious diseases - bleeding due to hepatorenal function disturbing Internal diseases - autoimmune diseases,liver,complication of analgetic in leptospirosis, hepatitis of different types,meningitis and anticoagulant treatment 3.14 Bleeding into joint a musculosceletal systm in are trauma origins and is specially important in bleeding disorders. Repeated hemartros in hemofilia causes infectious complications and ankylosis with movement troubles. 3.15.Bleeding into peritoneal and reproteritoneal cavity.Blunt abdominal trauma causes rupture of spleen, liver or kidneyas. Clinical picture is peritoenal signs and shock,high leucocyte count is present and patient should be carefully observed for urgent laparotomy. In various bleeding disorders and infectious mononucleosis rupture of these organs can be seen after minor or innocent trauma (spleen palpation) or spontaneously. Also bening or malignant tumors present in abdominal cavity can bleed spontaneously (liver adenoma, liver metastatic tumour nodule). 3.16.Bleeding of female reproductive organs - intraperitoneal or vissible through vagina ic caused by ectopic pregnancy and ovarial cysts.Signs of peritoneal iritation is seen. Careful personal history is necesssary and endoscopic investigation necessary.Laparotomy is frequently required. 3.17.Bleeing in tumors of various origins is caused by local destruction of tumour vesssels or surrounding tissue, coagulation defects in primary site or in metastatic site. 3.18 Elderly people bleed from various reasons due to occult malignant tumors, peptic ulcers due to often prescribed analgesics for arthrosis and ischemic heart diseaes (acylpyrin).Also atherosclerotic vessel malformation in often seen in colonic teleangiectasia, eye and nasopharyngeal reagion.

3.19 3.20 signs

Bleeing in childern appers in trauma and hematologic disease,epistaxis Head (Cranial) bleeding is often underdiagnosed due to nonspecific

often present.

dificulty in obtaining of valid personal history. Without careful investigation and followup with adequate treatment has high mortality. CT scan is very helpful.These bleeings occurs in various anatomical localities : epidural, subdural, intrameningeal and intraparenchymatous with different clicinal manifestation. The cause of bleeding is traumatic very often silent in alkoholic patients covered by intoxication symptoms. The cerebrovascular bleeding occurs due to atherosclerotic disease,hypertension and bleeding disorders. Neurological signs with changes of pupila and eye fundus is helpful, limbs movement assesment and regular follow up od the state of conciousness is also important. 3.20 Bleeding disorders Low level of platelets is caused by decreasing of production,increasing destruction due to immunogeni or non-immunogenic causes,sequestration of platelet in spleen is caused by portal hypertension, myeloproliferative and lymfoproliferative disorders. Often induced by drugs as neoplastic chemotherapy,thiazid diuretics,etanol and heparin treatment. Drug withdrawal is mostly helpful. Idiopathic tromcocytopenic purpura (ITP) is cured by steroid,plasmafersis,splenectomy and platelet transfusion. Vessel wall increased permeability is a cause of trombotic trombocytopenic purpura Schoenlein Henoch (TTP)and is manifested mostly after various streptococcal disease. Protein coagulation defect is inborn and geneticaly trasnmitted in hemofilia,aquired defect is seen in various liver diseases,disseminated intravsacular coagulation and deficit of vitamin K in small bowel disease or during coumarine anticoagulant treatment. 3.20 Disorders of blood coagulation Diagnosis of bleeding. Blood count and blood smear changes during bleeding. For investigation of bleeding disorders necessary is platelet count, bleeding time,which is test of unction.For quality of platelets exist various general and special test for proving of adhesion and agregation defect et c. Coagaulation tests include partial tromboplastin time (PTT),tromboplastin time (PT or Quick test),plasma fibronogen,assesment of fibrinolytic systm function (coagulum lysis), alfa 2 plasmin inhibiotor,defect of factor VIII.Biochemical blood test invlude

urea blood test.Assesment of volume of depleted blood can be assesed by monitoring of central venous pressure (CVP), provided by catheter placed in central vein. Hemorhagic shock is studied in animal model but not all results can be trasnefrred to human.Definition of shock. Regulation of arterial blood pressure (organ perfusion,cardiac output,blood volume,heart frequency,sytemic vascular resistence,blood viscosity,vaodilators and vasopressoric agents,renin.-angiotensin systm,kinins,prostaglandins.The types of shock (posthemorhagic,septic,anafylactic, cardiac,hypovolemic) its clinical manifestation and pathophysiology.Diagnostic and monitoring measures.Shock complication : adult respiratory distress syndrom (ARDS),renal failure,disseminated intravascular coagulation, multiorgan failure, a its monitoring by blood gases,fibrin degradation products et c and treatment 4.8.Methods of investigation on bleeding. Endoscopic methods in gastroenterology and other methods Eye examination ( fundus, magnifying glass) ENT examination - speculum,endoscopy Neurologic investigation - pupila,reflexes,assesment of consciousness,meningeal signs, Traumatologi investigation of musculoskeletal systm - X ray and CT scan Female genital investigation Urology investigation - cystoscopy,X-ray,urine exam Abdominal investigation by surgeon Imaging methods X ray investigation - plain film, CT scan,X-ray investigation with contrast agent (IV uropraphy),angiography and its usefulness in acute and chronic bleeding indication,possibilities,technical measures, treatment by this method,CT scan,NMR Radionuclide methods - marked red cells,Meckel diverticulum scan,ELISA methods Other methods 5.Treatment 5.1 Blood and blood derivates tranfusion.Absolute and relative indication.Adverse

events serious (inkompatibility of blood groups),infection,alergy,its diagnosis and

treatment and prevention.Indication for whole blood ,plasma and ,red packed cell transfusion. 5.2 Transfusion of defective factors - platelet and white blood cells transfusion,its

indication a usefulness 5.3 Other liquids for infusion - saline, plasmaexpanders (its composition,indication,

function and usefulness 5.4 Treatment of bleeding disorders Substitution of the missed factors during bleeding Preventive treatment for repeated bleeding

5.4.1 5.4.2 5.5 5.6 5.7 5.8

Infusion of blood plasma and its derivates Hemostyptic therapy - choice,power,indication Treatment of hemoptysis - konservative and surical Treatment of oesophageal varices bleeding - endoscopy sclerotisation and

ligation,Sengstaken baloon tamponade, vasopressin,TIPS (transjugular portosystemic shunt) 5.8.1. 5.8.2. 5.8.3. 5.8.4. 5.8.5. 5.9. General measures - shock treatment,blood transfusion, Endoscopic sclerotisation by needle method with 90% succes Surgical methods - portocaval anastomosis today rarely done, Interventional radiology - TIPS Medicamentous treatment - vasopresin,blood derivates,somatostatin

Treatment of upper gastrointestinal bleeding except varices 5.9.1. 5.9.2. Endoscopy therapy Surgical treatment - acute and elective operations injection,laser,photocoagulation,electrocoagulation

5.10.Treatment of lower gastrointestinal bleeding - usually not severe,mostly stops after blood tranfusion.Surgical therapy only for progressive hemorhage in acute phase,but usually elective treatment after stoppping bleeding.Diagnosis by endoscopy or angiography. 5.11.Treatment of intracranial bleeding

5.11.1.Conservative - antioedematic treatment,symptomatic 5.11.2.Surgical -after unsucesful conservative treatment, traumatic etiology (epidural,subdural bleeding,anatomy of intravascular vessels,diagnosis and types of operations) 6.Prevention of bleeding 6.1.1Prevention of bleeding disorder inborn errors - genetic screening, acquired - mostly preventive medicamentous treatment 6.1.2.Drugs caused bleeding a mechanism of action - analgesics, anticoagulant (checking of laboratory tests,frequency,practical aspects in surgery,prevention of complication),other drugs (steroids,theophylin) 6.1.3.Prevention of oesophageal bleeding - mostly medicamentous (propranolol),profylactic surgery due to high mortality and complication rate is not reccomended.Before liver transplantation and after repeated bleeding mostly transjugulars portosystemic anastomosis is used.