Nonmalignant Hematologic Disorders Part Two Chapter 33 Anastasia Harlan, MSN, RN Polycythemia Secondary Polycythemia • Excess RBCs Polycythemia • Elevated Hct – greater than 55% in males and 50% in females • Dehydration can cause elevated hematocrit not usually associated with polycythemi a • Primary (polycythemia vera) – is a proliferative disorder and will be discussed in Chapter 34 • Secondary polycythemia • Caused by excessive production of erythropoietin • Reduced oxygen (hypoxic events) • Heavy cigarette smoking • OSA • COPD • Cyanotic heart dz • High altitude • Exposure to low levels of CO • Hemoglobinopathies • Hgb has high affinity for O2 or • Genetic mutations causing high erythropoietin levels causing erythropoiesis • Neoplasms (renal cell carcinoma) • Medical Management • Mild – no tx. Treat primary condition. • Symptomatic – therapeutic phlebotomy unless elevated RBCs are in response to tissue hypoxia • Excessive production of erythropoietin Secondary Polycythemia • May be a response to low O2 • Heavy cigarette smoking • OSA • COPD • Cyanotic heart disease • High altitude living • Exposure to low levels of carbon monoxide • May be response to hemoglobinopathies • Hgb Chesapeake – Hgb has high affinity for O2 from genetic mutation • Neoplasms – i.e., renal cell carcinoma • Treatment • Depends on severity and cause Bleeding Disorders Secondary Thrombocytosis Thrombocytopenia Immune Thrombocytopenic Purpura Platelet Defects Hemophilia Von Willebrand Disease (vWD) Bleeding Disorders • Trauma • Spontaneously • Platelet • Bleeding can be severe, may be controlled with pressure • Coagulation factor abnormalities • Bleeding occurs deep within the body • Vascular abnormalities • Localized bleeding usually to skin petechiae • Thrombopoiesis • The balance between the two systems of thrombus (clot) formation and fibrinolysis (clot dissolution) Hemostasis • Primary mechanism is increased platelet production • Plt count above normal Secondary Thrombocytosis (Reactive thrombocytosis) • Plt function normal • Plt survival time normal or decreased • Sx associated with hemorrhage or thrombosis are rare • Treat underlying disorder Thrombocytopenia • Low platelet level r/t • Decreased platelet • Nursing Management production in marrow • aplastic anemia, megaloblastic anemia, toxins, meds, infection, ETOH abuse, chemo, liver dz • Increased platelet destruction • ITP, CLL, meds, infection • Increased platelet consumption • DIC, major bleeding, severe PE, severe thrombosis, intravascular devices, ECMO (Many causes – see Table 33-3 pg. 948) • Plt cnt • < 20,000/mm3 – petechiae; nasal/gingival bleeding; excessive bleeding with menses, post-op, dental extractions • < 5000/mm3 – spontaneous, potentially fatal CNS or GI hemorrhage • Meds may potentiate adverse effects of low plts Thrombocytopenia • Assessment & Diagnostic Findings • Bone marrow aspiration/bx • Genetic component • Screen for Hep B/C • Ensure CBC specimen not clotted • Medical Management • Tx underlying cause • PRBC or plt transfusion • Meds: corticosteroid • Splenectomy • Affects all ages, more common among children Immune Thrombocytopenia Purpura - ITP inhibit plt production in marrow • aka: idiopathic • Primary ITP thrombocytopenia purpura • Occurs in isolation & immune • Platelet count thrombocytopenia less than 100 x • Autoimmune d/o that 109/L with destroys normal platelets inexplicable for unknown cause absence of cause • Antiplatelet antibodies bind to • Secondary ITP plts which are then • Results from ingested and • autoimmune destroyed by RES diseases – • Body attempts to antiphospholip compensate by id antibody increasing plt syndrome production in • Viruses – marrow hepatitis C, HIV • Antibodies induce • Drugs - sulfa cell death via apoptosis of megakaryocytes and Immune Thrombocytopenic Purpura - continued • Clinical Manifestations • Dry purpura • Often no sx • Simple bruising or petechiae • Low plt count an incidental finding • Fewer complications • Easy bruising, heavy menses, petechiae • Treatment may not begin until bleeding is severe or life-threatening • Wet purpura • Bleeding of mucosal surfaces: GI • Assessment & Diagnostic Findings tract, pulmonary system • Identify bleeding • Higher risk of problems • Test for Hep C, HIV, Helicobactor pylori • Requires prompt, aggressive tx • Need neuro consult ITP CONT • Medical Management • Obtain safe plt count • Determine cause: if med, discontinue • Immunosuppressant drugs to block binding receptors on macrophages to stop platelet destruction • IVIG in high doses • Splenectomy • Monoclonal antibodies • Nursing Management • ID OTC meds, herbs, supplements, ASA, NSAIDs • Recent viral illness, H/A, visual disturbances, IC bleeding • Monitor plt cnt • Educate to • Avoid constipation, flossing • Use electric razor, soft bristle toothbrush • Avoid rigorous sex • X linked disorder • Mostly males • Females carriers, generally asymptomatic • 1/3 of cases from spontaneous mutations rather than familial • All ethnic groups Hemophilia • Relatively common • Hemophilia A • Genetic defect resulting in deficient or defective factor VIII • Occurs in 1 out of every 5000 – 7000 births • 5X more common that Hemophilia B • Hemophilia B (Christmas disease) • Genetic defect causing deficient or defective factor IX Hemophilia (continued) • Severe • Plasma factor level 1 IU/dL or less or Factor VIII levels < 1% spontaneous hemorrhage, hemarthroses, hematomas • Moderate • Plasma factor level 1-5 IU/dL or Factor VIII level 1 - 5% • Mild • Plasma factor level > 5 IU/dL or Factor VIII level > 5% rarely develop spontaneous hemorrhage Hemophilia (continued) • Clinical Manifestations • Hemorrhages in various body parts • Can be severe • Can occur after minimal trauma • Frequency and severity depends on degree of factor deficiency + intensity of trauma • Mild factor VIII deficiency rarely develop spontaneous hemorrhage; hemorrhage is secondary to trauma • Severe factor VIII deficiency develop spontaneous hemorrhages – hemarthroses and hematomas • 75% of bleeding occurs in joints: knees, elbows, ankles, shoulders, wrists, hips • Associated complications of joint bleeding: chronic pain, ankylosis, arthropathy, disability • Other bleeding: GI, head • Fall risk HEMOPHILIA CONT • Medical Management • FFP • Recombinant factor VIII, X concentrates • Prophylactic measures prior to procedures involving puncture, extraction • Nursing Management • Childhood diagnosis • Coping strategies • Prevent unnecessary trauma Von Willebrand Disease (vWD) • Most cases are autosomal • Type 2 dominant (abnormal gene from • Several subtypes one parent; children have 50% • vWF does not function chance of obtaining) properly • Autosomal recessive (type • More significant s/sx 3) – both parents pass gene to child • Type 3 • Males and females equally • vWF absent affected • Low factor VIII • 1-2% of population have vWD • Severe s/sx; bleeding into joints and muscles • Caused by low levels of von Willebrand factor (vWF) protein • Acquired von Willebrand disease which causes platelets to not • Not inherited – develops stick together, not attach to later in life vessel wall, and cause uncontrolled bleeding in some • Complications cases • Anemia • Type 1 • Swelling and pain • most common form • Death from bleeding • Low levels of vWF • Low factor VIII • Mild s/sx Von Willebrand Disease (continued) • Clinical Manifestations • Mucosal bleeding typical • Assessment & Diagnostic Findings • Medical Management • History of bleeding since childhood • Replace deficient vWF or factor VIII at • Reduced vWF activity in plasma time of spontaneous bleeding or prior to procedures (Humate-P and Alphanate) • Hx of bleeding in family • Desmopressin used for dental/surgical • Normal plt cnt, prolonged bleeding time, procedures to manage post-op bleeding slightly prolonged aPTT (IV or intranasally) • Values vary over time Acquired Coagulation Disorders Liver Disease Vitamin K Deficiency Disseminated Intravascular Coagulation Thrombotic Disorders Hyperhomocysteinemia Antithrombin Deficiency Protein C Deficiency Protein S Deficiency Activated Protein C Resistance and Factor V Leiden Mutation Acquired Thrombophilias Liver Disease • Most blood coagulation factors are synthesized in liver (not factor VIII) • Hepatic dysfunction can diminish factors needed for coagulation and hemostasis • Cirrhosis • Tumor • Hepatitis • PT prolongation caused by Vit K deficiency may indicate severe liver dysfunction https://youtu.be/1UUQylgW9aM INR • Risk – ecchymosis or severe bleeding • Tx – FFP • If GI bleed, FFP, PRBC, plts Vitamin K Deficiency • Common in malnourished patients • Result of warfarin therapy • Can be result of prolonged use of abx reducing intestinal flora which stores Vit K • Treat with phytonadione orally or sq • https://youtu.be/tY28cQSBy3g PT Disseminated Intravascular Coagulation (DIC) • Not a disease, but a condition of progressively decreasing platelets caused by underlying condition • Triggered by sepsis, trauma, cancer, shock, abruptio placentae, toxins, allergic reactions, and others • Mostly infection or malignancy • Severity variable, potentially life-threatening • Decline of organ function from excessive clot formation followed by excessive bleeding when anticoagulation factors are used up DIC Pathophysiology https://youtu.be/Gmh01S0msfY • Normal hemostatic mechanisms are altered • Inflammatory process activated by underlying disease • Inflammation and coagulation in vasculature • Natural anticoagulation pathways in body simultaneously impaired • Fibrinolytic system suppressed • Massive amounts of tiny clots form in microcirculation • Initially coagulation time is normal • As platelets and clotting factors form microthrombi, coagulation fails • Paradoxical result of excessive clotting and bleeding DIC Pathophysiology (continued) • Primarily reflected in compromised organ function or failure • From excessive clot formation causing ischemia to parts or all of organ • Excessive clotting triggers fibrinolytic system to release fibrin degradation products • Potent anticoagulants --- further contribute to bleeding • Bleeding characterized by low platelets, low fibrinogen levels, prolonged PT, aPTT, and thrombin time; elevated fibrin degradation products and D-dimers • Mortality rate 80% in pts with ischemic thrombosis, frank hemorrhage, and multi organ dysfunction syndrome (MODS) • Primary prognostic factor is treating underlying condition that precipitated DIC • https://youtu.be/MOGod7tHb18 aPTT Clinical Manifestations of DIC • Bleeding occurs from mucous membranes, venipuncture sites, GI and urinary tracts • Bleeding ranges from minimal occult internal bleeding to profuse hemorrhage from all orifices • Initially, there may be no symptoms except for decreasing platelet count • As thrombosis intensifies, outward symptoms begin • Signs and symptoms depend on organ involved – see pg. 957 • Common lab value trends found in DIC: • • • • • • • • Platelet ↓ PT ↑ aPPT ↑ TT ↑ Fibrinogen ↓ D-dimer ↑ Fibrin degradation products ↑ Euglobulin clot lysis < 1 hour DIC Medical Management • Aggressively treat underlying cause • Correct secondary effects of tissue ischemia • O2 • Fluid replacement • Correct electrolyte imbalances • Administer vasopressor meds/gtts • For severe hemorrhage, replace • Coagulation factors • Cryoprecipitate for fibrinogen and Factors V and VII • FFP – can exacerbate capillary leakage compromised pulmonary function • Platelets • LMWH – may reduce microclots in organ(s) DIC Nursing Management • Be aware of pts at risk for DIC • • • • Sepsis Surgery & trauma Cancer Serious complications of pregnancy and childbirth • Poisonous snake bites • Frostbite • Burns • Frequent VS, thorough assessments, monitor bleeding indicators & lab trends • For pt with DIC • • • • • • • • • • • • • Monitor hemodynamics Perform frequent assessment Measure abdominal girth Closely monitor I&O Avoid meds interfering with plt fxn Avoid rectal probes/meds Avoid IM Monitor dressings Assess secretions Monitor sanitary pad or other pad Use low pressure suctioning Swabs for oral hygiene Avoid dislodging clots Thrombotic Disorders • Conditions that alter balance of normal hemostasis • Arterial • Platelet aggregation • Venous • Platelets, RBCs, thrombin • May occur as initial manifestation of occult malignancy or complication from pre-existing cancer • Predispositions • Clotting inhibitors in circulation • Altered hepatic function • Lack of fibrinolytic enzymes • Tortuous or atherosclerotic vessels • Inherited or acquired conditions Hyperhomocysteinemia • • • • Can be hereditary or result from nutritional deficiencies (folate, B12, B6) Older adults and those with kidney disease susceptible to elevated homocysteine Vessel walls are denuded precipitating thrombus formation Homocysteine • Promotes platelet aggregation • Increases risk for venous thromboembolism (VTE), DVT, PE, recurrent VTE, arterial thrombosis (ischemic stroke, ACS) • Testing • Patient consumes methionine and blood levels obtained 4 hours later • Teach pts to refrain from smoking as B6, B12, and folate are lowered allowing homocysteine levels to rise • Supplements do not help treat Antithrombin Deficiency (AT) • Protein that inhibits thrombin and some coagulation factors contributing to venous thrombosis • AT level less than 60% of normal • Common site of thrombosis is leg and mesentery • Hereditary – test family members • Pt may become heparin resistant and require higher amount for adequate anticoagulation • AT deficiency can be acquired from • Accelerated consumption of AT(DIC) • Reduced synthesis of AT (hepatic fxn) • Increased excretion of AT (nephrotic syndrome) • Medication induced (estrogen, L-asparaginase) Protein C Deficiency • Vitamin K-dependent enzyme synthesized in the liver • Inhibits coagulation when activated • Risk of thrombosis increases with deficient protein C • Asymptomatic until 20+ years of age • Thrombotic event risk increases • High risk for recurrent PE • Complications: warfarin-induced skin necrosis • Stop warfarin • Administer Vit K • Infuse heparin and FFP • Natural anticoagulant produced by liver • Activated protein C (APC) requires protein S to inactivate some clotting factors Protein S Deficiency • If protein S deficient, risk of thrombosis increases • Risk for DVT and recurrent PE • Thromboses common in axillary, mesenteric, cerebral veins • Warfarin-induced skin necrosis possible • Protein S Deficiency seen in pregnancy, DIC, liver dz, nephritic syndrome, HIV infection, use of L-asparaginase Activated Protein C Resistance and Factor V Leiden Mutation • Common condition occurring with hypercoagulable states • An anticoagulant • Resistance increases risk of venous thrombosis • Caused by molecular defect in factor V gene in 90% of pts • Factor V Leiden mutation most common cause of inherited hypercoagulability in Caucasians • Incidence lower in other ethnic groups • Factor V Leiden synergistically increases risk of thrombosis in pts with other risk factors: • Oral contraceptives • Hyperhomocysteinemia • Older age • People are homozygous for factor V Leiden mutation have extremely high risk for thrombosis (80 fold increase) and need anticoagulation for life • People who are heterozygous for mutation have lower chance of thrombus • Duration of anticoagulation based on coexistence of other clotting risk factors • https://youtu.be/08jsvQ4sJZg heterozygous & homozygous alleles Acquired Thrombophilia Antiphospholipid Syndrome • Not inherited • Affects women more than men • Occurs when immune system produces antibodies that make blood more likely to clot • Syphilis • AIDs • HIV • Hep C • Lyme dz • Results from inappropriate clot formation caused by either an: • Excess of antibodies that cause clotting or • Increase in clotting factors • Can be caused by underlying condition • Autoimmune d/o • Infection • medications • S/Sx Antiphospholipid Syndrome • DVT • Repeated miscarriages or stillbirths • Stroke • TIA • Rash • Less commonly • Neuro sx • CVD • Bleeding Acquired Thrombophilia Malignancy • Cancers – most commonly • • • • Stomach Pancreatic Lung Ovarian • Clot occurs in unusual sites • • • • Portal vein Hepatic vein Renal vein Inferior vena cava • Migratory superficial thrombophlebitis or nonbacterial thrombotic endocarditis can also occur • Anticoagulation can be difficult to manage • Thrombosis may progress despite therapy • LMWH appears to be more effective than warfarin Meds & Substances Impairing Platelet Function References • CDC Sickle Cell Disease. Data & Statistics on Sickle Cell Disease https://www.cdc.gov/ncbddd/sicklecell/data.html • Iron Disorders Institute: Iron tests http://www.irondisorders.org/iron-tests • Mayo Clinic Antiphospholipid syndrome https://www.mayoclinic.org/diseasesconditions/antiphospholipid-syndrome/symptoms-causes/syc-20355831 • Mayo Clinic Sickle Cell Anemia https://www.mayoclinic.org/diseasesconditions/sickle-cell-anemia/symptoms-causes/syc-20355876 • Mayo Clinic von Willebrand Disease https://www.mayoclinic.org/diseasesconditions/von-willebrand-disease/symptoms-causes/syc-20354978 • NIH Sickle cell disease. Genetics Home Reference https://ghr.nlm.nih.gov/condition/sickle-cell-disease • Oldways: Vegetarian and vegan vitamin B12 food sources (2018). https://oldwayspt.org/blog/vegetarian-and-vegan-vitamin-b12-food-sources
