Bleeding in Palliative Care - Oxford

Question 1

Etiology of bleeding in advanced cancer/disease

Answer 1

1. Cancer invasion or destruction
   
   1. RCC, choriocarcinoma
2. Treatment related causes
   
   1. prior RT or surgery damage mucosa
   2. mucositis from chemo/rt
   3. BMT, graft vs host disease
   4. chemo thrombocytopenia
   5. MAHA mitomycin
   6. Post RT telangectasia of bladder, cervix, prostate
   7. hemorrhagic cystitis cyclophosphamide
3. Thrombocytopenia / marrow failure
   
   1. ​marrow suppression
   2. DIC
4. Nutritional deficits
   
   1. ​folate, B12, Vit K
5. Drugs
   
   1. NSAIDS, Warfarin,
   2. Thrombocytopenia : septra, cimetidine, ranitidine, acetaminophen, carbamazepine, mirtazipine, heparin.
6. Coagulation disturbances
   
   1. ​ITP, Goodpastures

Question 2

Definition of Massive Hemorrhage

Answer 2

Massive arterial hemorrhage:

> 1.5 L of blood in 30 seconds which will cause death in minutes

Massive hemoptysis

> 200 ml in 24 hours causing hemodynamic or respiratory compromise or hematocrit < 0.30

Carotid Blow Out Syndrome (CBO)

• proximal to carotid bifurcation
• soft tissue necrosis of neck
• Mucocutaneous fistulas
• Threatened (clinically or radiographically visible), impending (herald bleed) or acute (rupture)

Question 3

Risk factors for bleeding in cancer patients

Answer 3

• Thrombocytopenia < 20
• Large head and neck ca
• Large central lung cancers
• Leukemias
• Myelodysplasia
• Severe liver disease
• Metastatic liver disease
• HCC
• Oral anticoagulants
• High dose radiation therapy

Question 4

Risk factors for terminal/ massive hemorrhage in head and neck cancers

Answer 4

• radical neck dissection
• high dose RT
• Post operative wound complications
• visible arterial pulsation
• pharyngocutaneous fistula
• fungating tumours with arterial invasion
• Direct observation during surgery or imaging of arterial invasion
• Sentinel bleed

Question 5

General Management of Bleeding

Answer 5

• Clarify goals of care / communication
• History and physical
  
  • medications, wounds, multiple vs single sites
• Investigations
  
  • CBC, platelets, INR, PTT, fibrinogen
  • Endoscopy, angiography, MR, etc
• Prevention
  
  • wound care: non adherent dressings
  • stents
  • BB in varices
• Treatment

Question 6

Local treatment of bleeding

Answer 6

• Compression dressing and packing
• Topical hemostatic agents
  
  • Absorbable agents: gelatin foam, oxidized cellulose, microfibrillar collagen
  • Alginates : minor bleeds, useful for exudates, not major bleeding. Pads/ribbons form sodium alginate and calcium which supports normal clotting. Support auto debridement. Washes away.
  • Astringents, sclerosing and vasoconstrictor agents
    
    • silver nitrate, alum, sucralfate, formalin, epinephrine, cocaine
    • Silver nitrate : oxidixing agent causes tissue coagulation
    • Alum : precip of protein in interstitium results in vasoconstriction, hardening of capillaries. Avoid in renal failure, large bladder tumours.
    • Sucralfate : produces PG and proliferation of epithelial calls. Enemas bid for rectal bleeding, 1g tablets mixed with KY gel to make a paste for wounds.
  • Synthetic agents: cyanoacrylate
  • Hemostatic dressings: fibrin dressing
  • Topical TXA, steroid suppositories
    
    • ​TXA tablets or inj soaked gauze directly applied to wound
    • Moh’s paste (zinc chloride)
  • Biologic agents : topical thrombin, fibrin sealants, platelet sealants (limited utility)
• Radiation therapy
• Endoscopy / bronchoscopy
  
  • Upper and lower GI / lung tumours
  • Electrocautery, laser, argon plasma, cryotherapy
  • Balloon tamponade, injection of vasoconstrictor, irrigation
• Transcatheter arterial embolization (TAE)
  
  • femoral/ axillary approach with arteriogram and superselection of vessel
  • coils, microspheres, gelfoam, alcohol
  • Bronchial artery embolization for massive hemoptysis
  • Internal iliac or bladder artery embolization for bladder or pelvic hemorrhage
  • head and neck cancers, adrenal artery
  • Post embolization syndrome: nausea, vomiting, pain and fever from tissue necrosis
• Surgery
  
  • ligation of artery, fulguration, resection
  • cystectomy for severe hemorrhagic cystitis
  • carotid ligation (!), pulmonary resection (!)

Question 7

Systemic modalites of treating bleeding

Answer 7

• Antifibrinolytic agents : block plasminogen conversion to plasmin. Decreased lysis of clots.
  
  • Tranexamic Acid
    
    • 1.5 g po tid to maximum of 2 g qid
    • TXA 10 mg/kg IV over 5-10 min
  • Aminocaproic acid
    
    • 5 g loag, 1g po qid (max dose 30g /day)
    • 4g IV in 250cc NS until bleeding stops
  • SE : nausea, vomiting, diarrhea. Thromboembolim uncommon
  • Renal dosing required
  • Avoid in DIC. Caution in hematuria –> clot obstruction
• Somatostatin Analoges (Octreotide)
  
  • UGIB bleeds variceal, PUD
  • reduces splanchnic flow, portal pressure and venous flow by causing venous dilatation
  • 50-100 sc/iv bid-tid. Bolus 50 ug and infusion of 50 ug/hour
  • SE: abdominal pain, nausea, diarrhea
• Vasopressin Analogues
  
  • Vasopression posteriro pituitary hormone
  • causes splanchnic arteriolar constriction, reduced portal pressure
  • DDAVP for various bleeding in malignancy
    
    • GI, heme, thrombocytopenia small pilot study
    • Desmopression 0.4 ug/kg in 100 ml NS over 30 minutes
    • Aerosolized DDAVP for hemoptysis described
• Vit K
  
  • fat soluble vit for production of factors II, VII, IX, X.
  • Liver disease, decreased intake, small bowel disease, biliary obstruction – deficiency
  • Indications:
    
    • bleeding from oral AC, liver disease and DIC
  • Oral preferred : more reliable, fewer adverse effects
    
    • INR < 5 : hold warfarin
    • INR 5-10 : hold warfarin, give 2.5 mg vit K orally
    • INR >10 : hold warfarin, give 2.5-5 mg vit K orally
  • Bleeding, need for procedure:
    
    • IV Vit K
    • FFP 4-5 units
    • poss recombinant factor VIIa
• Blood and plasma products (see next slide)
  
  • platelets > 50 x10(9) okay for procedures
  • Consider transfusion if < 10-20x10(9)
  • Prophylaxis with aminocaproic acid?
• FFP
  
  • contains all clotting factors
  • urgent reversal in liver disease, DIC, warfarin for procedures or big bleed
  • INR > 1.6
  • Dose 15 ml/kg (4 units)
  • volume overload, do not use in hemophilia B
• Cryoprecipitate
  
  • thawed FFP contains factor VII and fibrinogen, vW factor, factor XIII
  • indicated in bleeding or procedures where low fibrinogen, vWD, hemophilia A, factor XIII, uremia with bleeding
  • 2 units / 10kg
• Recombinant coag factors (VIIa, VIII, IX)
  
  • massive trauma, hemophilia, liver disease
• ​Hyperbaric 02
  
  • ​promotes granulation tissue and neovascularization
  • multiple treatments up to 90 min
  • CI : active cancer, viral infection, pneumothorax, cisplatin/doxorubicin, ear reconstruction
• Others
  
  • pentosanpolysulphate, thalidomide, melatonin

Question 8

Platelet transfusion

Answer 8

• No consensus - Cochrane review
• consider prophylactic transfusion < 10-20 x 10(9)
  
  • or with bleeding / risk factors
• need > 50 x 10 (9) for procedures/surgery
• need > 100 x 10(9) for neurosurgery/opthalmic sx
• short life span 3-4 days, half life drops as platelet count drops
• immune mediated refractoriness
  
  • anti HLA antibodies
• Indications for transfusion in hematologic malignancies
  
  • continuous bleeding mouth / gums
  • overt hemorrhage
  • extensive painful hematoma
  • disturbed vision
  • severe headache
  • severe anemia
• Ethical challenges with platelet transfusion at end of life.
  
  • frequency, logistics
  • alleviate sx
  • SE: fever, alloimmunization, infection

Question 9

Terminal Hemorrhage

Answer 9

• supportive measures (dark towels, staying with patient, etc)
• general resuscitative measures (fluids, etc)
• Specific hemostatic measures prn

Sedatives (midazolam 2-10 mg sc/iv)

• lack of utility in literature
• detracts from being with patient
• not enough time to administer
• most important dark towel and being with patient

Question 10

Bleeding esophageal varices

Answer 10

• octreotide
• pantoloc
• erythromycin
• endoscopy for ligation, sclerotherapy
• TIPS
• Balloon tamponade (Sengstaken-Blakemore)

Question 11

Hemorrhagic Bladder

Answer 11

• Clot evacauation first
• 3 way catheter with CBI
• Alum instillation
• TXA, silver nitrate, prostaglandin, phenol instillation
• radiotherapy
• internal iliac artery embolization
• hyperbaric 02
• formalin instillation
• surgery / percutaneous nephrotomy / cystectomy

Question 12

Hemoptysis : definition

Answer 12

• definition unclear : > 300 cc single episode, 500 cc /24 hours
• needing resuscitation, or causing airway obstruction

Question 13

Hemoptysis : Causes

Answer 13

• bronchial artery supply majority of causes
• non bronchial systemic arterial system
• minority from pulmonary vessles
• infection
• neosplasm
• bronchiectasis
• CF
• cardiovascular disorders
• vasculitis
• trauma
• drugs (bevacizumab - monoclonol AB)
• coagulopathy
• thrombocytopenia
  *

Question 14

Hemoptysis : clinical approach

Answer 14

• airway protection
• volume resuscitation
• lateral decubitus position
• CBC, Cr, LFTs, PTT, INR
• CXray
• Bronchoscopy
• CT thorax prn

Question 15

Hemoptysis : management

Answer 15

• treat underlying disease / cause
• oncolgoic treatment
• radiotherapy
• correct coagulopathy
• discontinue medications that contribute (NSAIDS, AC)
• 02
• Tranexamic acid
• Recombinant activated factor VII
• endobronchial treatment with epinephrine, TXA, ADH, tamponade
• Endobronchial laser photocoagulation, argon plasma coagulation, electrocautery.
• Bronchial Arterial Embolization
  
  • failure of conservative treatment
  • massive recurrent hemoptysis
  • poor surgical risk
  • Risks: fever, dysphagia, groin hematoma, dissection or perforation of arteries, contrast nephropathy
• Surgery
  
  • BAE has failed
  • definitive treatment for some tumours