Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

classic PNH (haemolytic anaemia): non-pregnant

1st line – haemolysis control

Back
ACUTE
|
classic PNH (haemolytic anaemia): non-pregnant
1st line – 

haemolysis control

Eculizumab and ravulizumab specifically inhibit intravascular haemolysis in paroxysmal nocturnal haemoglobinuria (PNH). They improve anaemia in most patients, abolish symptoms due to nitric oxide deprivation, and rapidly relieve fatigue.[25][26]​​​ Eculizumab is given as long as the patient has haemolysis (usually, lifelong). Biosimilars of eculizumab are available in some countries.[30][31]

The eculizumab the dosing regimen (administered once every 2 weeks) may pose a treatment burden and impact patient adherence. Additionally, around 25% of patients may experience breakthrough haemolysis, increasing the risk of thrombotic events and other potentially life-threatening complications related to intravascular haemolysis.

Ravulizumab, an alternative treatment option, achieves immediate, complete, and sustained inhibition of complement-mediated haemolysis with a longer dosing interval.

There is a low risk of meningococcal infection with both eculizumab and ravulizumab; all patients must be immunised at least 2 weeks before beginning treatment, according to current immunisation recommendations. Immunisation should be updated as long as the patient is receiving therapy. Antibacterial prophylaxis may be given in situations where treatment must start within 2 weeks of vaccination. Eculizumab and ravulizumab may only be available through Risk Evaluation and Mitigation Strategy (REMS) programmes to mitigate the risk of serious meningococcal infections.

Pegcetacoplan, a complement C3 inhibitor, is an option as a first-line agent or for patients who may not respond well to C5 complement blockade. Pegcetacoplan controls both intravascular and extravascular haemolysis.

In one phase 3 open label trial, pegcetacoplan demonstrated superiority over eculizumab in improving haemoglobin levels and clinical and haematological outcomes in patients with PNH (with a haemoglobin level below 105 g/L (10.5 g/dL), despite receiving stable doses of eculizumab for at least three months before entering the study).[33]​ Improved haematological outcomes attributable to pegcetacoplan persisted during 48 weeks of treatment.[34]

In an indirect comparison of individual patient data, pegcetacoplan was associated with significantly reduced lactate dehydrogenase (LDH) and increased haemoglobin from baseline, compared with eculizumab or ravulizumab, in complement inhibitor-naïve patients with PNH.[35]

Iptacopan is an oral complement factor B inhibitor that acts upstream of the C5 terminal pathway, preventing intravascular and extravascular haemolysis in patients with PNH. Iptacopan can be used as a first-line agent, or for patients who do not respond well to C5 complement inhibitors due to clinically significant extravascular haemolysis. Iptacopan is the first oral treatment for the management of adults with PNH.

In one phase 3 trial, patients who had received eculizumab or ravulizumab in a stable regimen for at least six months were randomised to receive oral iptacopan monotherapy or to continue anti-C5 therapy.[36]​ An estimated 82.0% of patients with PNH treated with iptacopan experienced an increase in haemoglobin levels by 20 g/L (2 g/dL) or more from baseline, compared with 2.0% of patients with PNH treated with eculizumab or ravulizumab.[36]​ An estimated 69.0% of patients treated with iptacopan reached a haemoglobin level of at least 120 g/L (12 g/dL) without transfusion of red blood cells, compared with 2.0% of patients who received eculizumab or ravulizumab.[36]

There is a risk of serious infections with pegcetacoplan and with iptacopan. All patients must be immunised against encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae) at least 2 weeks before beginning treatment, according to current immunisation recommendations. Immunisation should be updated as long as the patient is receiving therapy. Antibacterial prophylaxis may be given in situations where treatment must start within 2 weeks of vaccination.

Pegcetacoplan and iptacopan are only available through Risk Evaluation and Mitigation Strategy (REMS) programmes due to the risk of serious infections.

There is a risk of unprecedented intravascular breakthrough haemolysis with single agent proximal complement inhibitors such as pegcetacoplan and iptacopan.[37]​ Breakthrough haemolysis, necessitating a switch back to eculizumab, has been reported with single agent proximal complement inhibitors such as pegcetacoplan.[33][34]​ Prospective clinical trials are needed to determine the optimal management of breakthrough haemolysis associated with proximal complement inhibitors.[38]

Primary options

eculizumab: 600 mg intravenously once weekly for 4 weeks, then 900 mg once weekly for 1 week, followed by 900 mg every 2 weeks thereafter

OR

ravulizumab: dose depends on patient’s body weight; consult specialist for guidance on dose

OR

pegcetacoplan: 1080 mg subcutaneously every 2 weeks

More

OR

iptacopan: 200 mg orally twice daily

More

Plus – RBC transfusion

Back
ACUTE
|
classic PNH (haemolytic anaemia): non-pregnant
|
with Hb <85 g/L (<8.5 g/dL)
Plus – 

RBC transfusion

Treatment recommended for ALL patients in selected patient group

Patients may require transfusion with red blood cells if haemoglobin (Hb) falls to a level that is symptomatic (fatigue, shortness of breath, symptoms of heart failure), usually to <85 g/L (<8.5 g/dL). This is occasionally accompanied by a bout of haemoglobinuria due to destruction of the abnormal PNH cells. This can be prevented by removing white blood cells from the transfused unit through washing or appropriate filtering. Washing will also remove any residual complement from the cells.[48] Iron overload is not a problem in PNH patients, as chronic losses in urine result in iron deficiency even in heavily transfused patients.

Consider – erythropoiesis-stimulating agents

Back
ACUTE
|
classic PNH (haemolytic anaemia): non-pregnant
|
with underlying aplastic anaemia and/or kidney damage
Consider – 

erythropoiesis-stimulating agents

Additional treatment recommended for SOME patients in selected patient group

Although endogenous erythropoietin (EPO) levels are usually high in PNH, supplemental injections of recombinant EPO have been found to be useful in some patients.[43][44]

Has been used in conjunction with eculizumab in a patient with underlying aplastic anaemia.[45] Also useful in patients with kidney damage due to PNH.[46]

If Hb has not increased by at least 10 g/L (1 g/dL) after 4 weeks at the initial dose of epoetin alfa, the dose may be increased if iron status is satisfactory.

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly initially, increase according to response, maximum 60,000 units/week

OR

darbepoetin alfa: 200 micrograms subcutaneously every 2 weeks, increase according to response, maximum 300 micrograms every 2 weeks

Plus – oral or parenteral iron replacement

Back
ACUTE
|
classic PNH (haemolytic anaemia): non-pregnant
|
with iron deficiency
Plus – 

oral or parenteral iron replacement

Treatment recommended for ALL patients in selected patient group

Patients with PNH lose up to 20 times as much iron per day as healthy people and may require supplementation with oral or parenteral iron. It is important to note that iron repletion may be followed by a brief episode of haemoglobinuria.[47]

Oral iron supplementation is an easy way to replace iron and is usually given in its elemental form. If patients cannot tolerate this or have such rapid iron loss that oral iron cannot keep up with the losses, iron can be given parenterally. Parenteral iron is generally safe, although severe cases of anaphylaxis have been reported.

Treatment is continued as long as iron stores, monitored by serum ferritin, are adequate and not excessive or haemolysis has been blocked by complement inhibitors.

Primary options

ferrous sulfate: 2-3 mg/kg/day orally given in 2-3 divided doses

More

Secondary options

iron dextran: consult specialist for guidance on dose

OR

sodium ferric gluconate complex: 125 mg intravenously once weekly for 8 weeks, maximum 1000 mg cumulative dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

Plus – thrombolysis

Back
ACUTE
|
classic PNH (haemolytic anaemia): non-pregnant
|
with thrombosis
Plus – 

thrombolysis

Treatment recommended for ALL patients in selected patient group

Thrombolytic agents such as urokinase or tissue plasminogen activator (tPA) may be used in acute stage of thrombosis, unless platelet count is <50,000/microlitre or thrombosis is intracranial.[49]

For cerebral thrombosis, anti-oedema therapy (usually dexamethasone or mannitol) and anticoagulation are used, but evidence is limited.

This should be followed by full anticoagulation with warfarin or heparin (preferably low-molecular-weight heparin).

Primary options

alteplase: 100 mg intravenously given over 2 hours

OR

urokinase: 4400 units/kg intravenously as a loading dose, followed by 4400 units/kg/hour intravenous infusion for 12 hours

OR

reteplase: 10 units intravenously initially, followed by 10 units 30 minutes later

classic PNH (haemolytic anaemia): pregnant

1st line – haemolysis control

Back
ACUTE
|
classic PNH (haemolytic anaemia): pregnant
1st line – 

haemolysis control

Eculizumab specifically inhibits intravascular haemolysis in paroxysmal nocturnal haemoglobinuria (PNH). It improves anaemia in most patients, abolishes symptoms due to nitric oxide deprivation, and rapidly relieves fatigue.[25][26]​​​​ Eculizumab is given as long as the patient has haemolysis (usually lifelong). Biosimilars of eculizumab are available in some countries.[30][31]

There is a lack of data on the use of ravulizumab, pegcetacoplan, and iptacopan in pregnancy.​​​ However, several recent reports describe successful outcomes for both mother and child with eculizumab.[39][40]​​​​ An analysis of 79 pregnancies involving 61 women receiving eculizumab during pregnancy demonstrated improved outcomes for the mother and fetus. All children achieved age-appropriate milestones. A higher dose of eculizumab was needed in the second and third trimester.[41]​ Anticoagulation should be given during the pregnancy and continued for at least 3 months postnatal.[42]​ 

There is a low risk of meningococcal infection with eculizumab; all patients must be immunised at least 2 weeks before beginning the treatment, according to current immunisation recommendations. Antibacterial prophylaxis may be given in situations where treatment must start within 2 weeks of vaccination.

Eculizumab may only be available through a Risk Evaluation and Mitigation Strategy (REMS) programme to mitigate the risk of serious meningococcal infections.

Primary options

eculizumab: 600 mg intravenously once weekly for 4 weeks, then 900 mg once weekly for 1 week, followed by 900 mg every 2 weeks thereafter

Plus – thromboprophylaxis

Back
ACUTE
|
classic PNH (haemolytic anaemia): pregnant
|
without thrombosis
Plus – 

thromboprophylaxis

Treatment recommended for ALL patients in selected patient group

Risk of thrombotic complications during pregnancy is high.[53] For this reason, anticoagulation with a low-molecular-weight heparin (LMWH) has been recommended. Patients should be started on a LMWH as soon as pregnancy is documented and continue treatment for at least 3 months postnatal.[42]

LMWH is considered optimal, having less risk than unfractionated heparin of heparin-induced thrombocytopoenia.

Warfarin is contraindicated in pregnancy due to its teratogenic effect.[54]

Primary options

enoxaparin: see local specialist protocol for dosing guidelines

OR

dalteparin: see local specialist protocol for dosing guidelines

Secondary options

heparin: see local specialist protocol for dosing guidelines

Consider – thrombolysis

Back
ACUTE
|
classic PNH (haemolytic anaemia): pregnant
|
with thrombosis
Consider – 

thrombolysis

Additional treatment recommended for SOME patients in selected patient group

There are no data to support thrombolytic therapy in pregnant women with PNH. Generally, systemic thrombolysis is considered risky in pregnant women, even though scant reports have shown encouraging outcomes with manageable complications in cases of life-threatening thrombosis.[52] Seek specialist guidance for management.

Plus – RBC transfusion

Back
ACUTE
|
classic PNH (haemolytic anaemia): pregnant
|
with Hb <85 g/L (<8.5 g/dL)
Plus – 

RBC transfusion

Treatment recommended for ALL patients in selected patient group

Patients may require transfusion with red blood cells if Hb falls to a level that is symptomatic (fatigue, shortness of breath, symptoms of heart failure), usually to <85 g/L (<8.5 g/dL). This is occasionally accompanied by a bout of haemoglobinuria due to destruction of the abnormal PNH cells. This can be prevented by removing white blood cells from the transfused unit through washing or appropriate filtering. Washing will also remove any residual complement from the cells.[48] Iron overload is not a problem in PNH patients, as chronic losses in urine result in iron deficiency even in heavily transfused patients.

Consider – erythropoiesis-stimulating agents

Back
ACUTE
|
classic PNH (haemolytic anaemia): pregnant
|
with underlying aplastic anaemia and/or kidney damage
Consider – 

erythropoiesis-stimulating agents

Additional treatment recommended for SOME patients in selected patient group

Although endogenous erythropoietin (EPO) levels are usually high in PNH, supplemental injections of recombinant EPO have been found to be useful in some patients.[43][44]​ EPO is generally considered to be safe in pregnancy, but there are no conclusive data of its use in pregnant PNH patients. The potential benefit must be weighed against the risk of thrombosis related to EPO use.

If Hb has not increased by at least 10 g/L (1 g/dL) after 4 weeks at the initial dose of epoetin alfa, the dose may be increased if iron status is satisfactory.

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly initially, increase according to response, maximum 60,000 units/week

OR

darbepoetin alfa: 200 micrograms subcutaneously every 2 weeks, increase according to response, maximum 300 micrograms every 2 weeks

Plus – oral or parenteral iron replacement

Back
ACUTE
|
classic PNH (haemolytic anaemia): pregnant
|
with iron deficiency
Plus – 

oral or parenteral iron replacement

Treatment recommended for ALL patients in selected patient group

Patients with PNH lose up to 20 times as much iron per day as healthy people and may require supplementation with oral or parenteral iron. It is important to note that iron repletion may be followed by a brief episode of haemoglobinuria.[47]

Oral iron supplementation is an easy way to replace iron and is usually given in its elemental form. If patients cannot tolerate this or have such rapid iron loss that oral iron cannot keep up with the losses, iron can be given parenterally. Parenteral iron is generally safe, although severe cases of anaphylaxis have been reported.

Treatment is continued as long as iron stores, monitored by serum ferritin, are adequate and not excessive or haemolysis has been blocked by complement inhibitors.

Primary options

ferrous sulfate: 2-3 mg/kg/day orally given in 2-3 divided doses

More

Secondary options

iron dextran: consult specialist for guidance on dose

OR

sodium ferric gluconate complex: 125 mg intravenously once weekly for 8 weeks, maximum 1000 mg cumulative dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

PNH in the setting of another specific bone marrow disorder: non-pregnant

1st line – treatment of underlying disorder

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: non-pregnant
1st line – 

treatment of underlying disorder

Marrow hypofunction in paroxysmal nocturnal haemoglobinuria (PNH) may be treated as in aplastic anaemia immunosuppressants.[55]

If immunosuppressants are ineffective, haematopoietic stem cell transplantation may be considered, particularly if a suitably matched related donor is available.[56][57][58]​ These measures become necessary if the platelet count and/or particularly the granulocyte count become too low (e.g., absolute neutrophil count <0.5×10⁹/L [<500/microlitre]).

Stem cell transplantation cures marrow hypofunction in PNH. When it is successful, all manifestations of the disease are eliminated. However, it carries the usual risk of death and chronic morbidity from chronic graft-versus-host disease.

See Aplastic anaemia.

Plus – RBC transfusion

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: non-pregnant
|
with Hb <85 g/L (<8.5 g/dL)
Plus – 

RBC transfusion

Treatment recommended for ALL patients in selected patient group

Patients may require transfusion with red blood cells if Hb falls to a level that is symptomatic (fatigue, shortness of breath, symptoms of heart failure), usually to <85 g/L (<8.5 g/dL). This is occasionally accompanied by a bout of haemoglobinuria due to destruction of the abnormal PNH cells. This can be prevented by removing white blood cells from the transfused unit through washing or appropriate filtering. Washing will also remove any residual complement from the cells.[48] Iron overload is not a problem in PNH patients, as chronic losses in urine result in iron deficiency even in heavily transfused patients.

Consider – erythropoiesis-stimulating agents

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: non-pregnant
|
with underlying aplastic anaemia and/or kidney damage
Consider – 

erythropoiesis-stimulating agents

Additional treatment recommended for SOME patients in selected patient group

Although endogenous erythropoietin (EPO) levels are usually high in PNH, supplemental injections of recombinant EPO have been found to be useful in some patients.[43][44]

If Hb has not increased by at least 10 g/L (1 g/dL) after 4 weeks at the initial dose of epoetin alfa, the dose may be increased if iron status is satisfactory.

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly initially, increase according to response, maximum 60,000 units/week

OR

darbepoetin alfa: 200 micrograms subcutaneously every 2 weeks, increase according to response, maximum 300 micrograms every 2 weeks

Plus – oral or parenteral iron replacement

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: non-pregnant
|
with iron deficiency
Plus – 

oral or parenteral iron replacement

Treatment recommended for ALL patients in selected patient group

Patients with PNH lose up to 20 times as much iron per day as healthy people and may require supplementation with oral or parenteral iron. It is important to note that iron repletion may be followed by a brief episode of haemoglobinuria.[47]

Oral iron supplementation is an easy way to replace iron and is usually given in its elemental form. If patients cannot tolerate this or have such rapid iron loss that oral iron cannot keep up with the losses, iron can be given parenterally. Parenteral iron is generally safe, although severe cases of anaphylaxis have been reported.

Treatment is continued as long as iron stores, monitored by serum ferritin, are adequate and not excessive.

Primary options

ferrous sulfate: 2-3 mg/kg/day orally given in 2-3 divided doses

More

Secondary options

iron dextran: consult specialist for guidance on dose

OR

sodium ferric gluconate complex: 125 mg intravenously once weekly for 8 weeks, maximum 1000 mg cumulative dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

Plus – thrombolysis

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: non-pregnant
|
with thrombosis
Plus – 

thrombolysis

Treatment recommended for ALL patients in selected patient group

Thrombolytic agents such as urokinase or tissue plasminogen factor may be used in the acute stage of thrombosis, unless the platelet count is <50×10⁹/L (50,000/microlitre) or thrombosis is intracranial.[49]

For cerebral thrombosis, anti-oedema therapy (usually dexamethasone or mannitol) and anticoagulation are used, but evidence is limited.

This should be followed by full anticoagulation with warfarin or heparin (preferably low-molecular-weight heparin).

Primary options

alteplase: 100 mg intravenously given over 2 hours

OR

urokinase: 4400 units/kg intravenously as a loading dose, followed by 4400 units/kg/hour intravenous infusion for 12 hours

OR

reteplase: 10 units intravenously initially, followed by 10 units 30 minutes later

PNH in the setting of another specific bone marrow disorder: pregnant with thrombosis

1st line – thrombolysis

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant with thrombosis
1st line – 

thrombolysis

There are no data to support thrombolytic therapy in pregnant women with paroxysmal nocturnal haemoglobinuria (PNH). Generally, systemic thrombolysis is considered risky in pregnant women, even though scant reports have shown encouraging outcomes with manageable complications in cases of life-threatening thrombosis.[52] Seek specialist guidance for management.

Plus – RBC transfusion

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant with thrombosis
|
with Hb <85 g/L (<8.5 g/dL)
Plus – 

RBC transfusion

Treatment recommended for ALL patients in selected patient group

Patients may require transfusion with red blood cells if Hb falls to a level that is symptomatic (fatigue, shortness of breath, symptoms of heart failure), usually to <85 g/L (<8.5 g/dL). This is occasionally accompanied by a bout of haemoglobinuria due to destruction of the abnormal PNH cells. This can be prevented by removing white blood cells from the transfused unit through washing or appropriate filtering. Washing will also remove any residual complement from the cells.[48] Iron overload is not a problem in PNH patients, as chronic losses in urine result in iron deficiency even in heavily transfused patients.

Consider – erythropoiesis-stimulating agents

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant with thrombosis
|
with underlying aplastic anaemia and/or kidney damage
Consider – 

erythropoiesis-stimulating agents

Additional treatment recommended for SOME patients in selected patient group

Although endogenous erythropoietin (EPO) levels are usually high in PNH, supplemental injections of recombinant EPO have been found to be useful in some patients.[43][44]​ EPO is generally considered to be safe in pregnancy, but there are no conclusive data of its use in pregnant PNH patients. The potential benefit must be weighed against the risk of thrombosis related to EPO use.

If Hb has not increased by at least 10 g/L (1 g/dL) after 4 weeks at the initial dose of epoetin alfa, the dose may be increased if iron status is satisfactory.

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly initially, increase according to response, maximum 60,000 units/week

OR

darbepoetin alfa: 200 micrograms subcutaneously every 2 weeks, increase according to response, maximum 300 micrograms every 2 weeks

Plus – oral or parenteral iron replacement

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant with thrombosis
|
with iron deficiency
Plus – 

oral or parenteral iron replacement

Treatment recommended for ALL patients in selected patient group

Patients with PNH lose up to 20 times as much iron per day as healthy people and may require supplementation with oral or parenteral iron. It is important to note that iron repletion may be followed by a brief episode of haemoglobinuria.[47]

Oral iron supplementation is an easy way to replace iron and is usually given in its elemental form. If patients cannot tolerate this or have such rapid iron loss that oral iron cannot keep up with the losses, iron can be given parenterally. Parenteral iron is generally safe, although severe cases of anaphylaxis have been reported.

Treatment is continued as long as iron stores, monitored by serum ferritin, are adequate and not excessive.

Primary options

ferrous sulfate: 2-3 mg/kg/day orally given in 2-3 divided doses

More

Secondary options

iron dextran: consult specialist for guidance on dose

OR

sodium ferric gluconate complex: 125 mg intravenously once weekly for 8 weeks, maximum 1000 mg cumulative dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

PNH in the setting of another specific bone marrow disorder: pregnant without thrombosis

1st line – thromboprophylaxis

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant without thrombosis
1st line – 

thromboprophylaxis

The risk of thrombotic complications in pregnant women with paroxysmal nocturnal haemoglobinuria (PNH) is high.[53] For this reason, anticoagulation with a low-molecular-weight heparin (LMWH) has been recommended.

Patients should be started on a LMWH as soon as pregnancy is documented and continue treatment for at least 3 months postnatal.[42]

LMWH is considered optimal, having less risk than unfractionated heparin of heparin-induced thrombocytopoenia.

Warfarin is contraindicated in pregnancy due to its teratogenic effect.[54]

Primary options

enoxaparin: see local specialist protocol for dosing guidelines

OR

dalteparin: see local specialist protocol for dosing guidelines

Secondary options

heparin: see local specialist protocol for dosing guidelines

Plus – RBC transfusion

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant without thrombosis
|
with Hb <85 g/L (<8.5 g/dL)
Plus – 

RBC transfusion

Treatment recommended for ALL patients in selected patient group

Patients may require transfusion with red blood cells if Hb falls to a level that is symptomatic (fatigue, shortness of breath, symptoms of heart failure), usually to <85 g/L (<8.5 g/dL). This is occasionally accompanied by a bout of haemoglobinuria due to destruction of the abnormal PNH cells. This can be prevented by removing white blood cells from the transfused unit through washing or appropriate filtering. Washing will also remove any residual complement from the cells.[48] Iron overload is not a problem in PNH patients, as chronic losses in urine result in iron deficiency even in heavily transfused patients.

Consider – erythropoiesis-stimulating agents

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant without thrombosis
|
with underlying aplastic anaemia and/or kidney damage
Consider – 

erythropoiesis-stimulating agents

Additional treatment recommended for SOME patients in selected patient group

Although endogenous erythropoietin (EPO) levels are usually high in PNH, supplemental injections of recombinant EPO have been found to be useful in some patients.[43][44]​ EPO is generally considered to be safe in pregnancy, but there are no conclusive data of its use in pregnant PNH patients. The potential benefit must be weighed against the risk of thrombosis related to EPO use.

If Hb has not increased by at least 10 g/L (1 g/dL) after 4 weeks at the initial dose of epoetin alfa, the dose may be increased if iron status is satisfactory.

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly initially, increase according to response, maximum 60,000 units/week

OR

darbepoetin alfa: 200 micrograms subcutaneously every 2 weeks, increase according to response, maximum 300 micrograms every 2 weeks

Plus – oral or parenteral iron replacement

Back
ACUTE
|
PNH in the setting of another specific bone marrow disorder: pregnant without thrombosis
|
with iron deficiency
Plus – 

oral or parenteral iron replacement

Treatment recommended for ALL patients in selected patient group

Patients with PNH lose up to 20 times as much iron per day as healthy people and may require supplementation with oral or parenteral iron. It is important to note that iron repletion may be followed by a brief episode of haemoglobinuria.[47]

Oral iron supplementation is an easy way to replace iron and is usually given in its elemental form. If patients cannot tolerate this or have such rapid iron loss that oral iron cannot keep up with the losses, iron can be given parenterally. Parenteral iron is generally safe, although severe cases of anaphylaxis have been reported.

Treatment is continued as long as iron stores, monitored by serum ferritin, are adequate and not excessive.

Primary options

ferrous sulfate: 2-3 mg/kg/day orally given in 2-3 divided doses

More

Secondary options

iron dextran: consult specialist for guidance on dose

OR

sodium ferric gluconate complex: 125 mg intravenously once weekly for 8 weeks, maximum 1000 mg cumulative dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

subclinical PNH: non-pregnant

1st line – monitoring

Back
ACUTE
|
subclinical PNH: non-pregnant
1st line – 

monitoring

Asymptomatic patients with small paroxysmal nocturnal haemoglobinuria (PNH) clones and no evidence of haemolysis (no anaemia) should be in periodic follow-up and be managed in the setting of emerging complications.

subclinical PNH: pregnant

1st line – thromboprophylaxis

Back
ACUTE
|
subclinical PNH: pregnant
1st line – 

thromboprophylaxis

There are no solid data on subclinical paroxysmal nocturnal haemoglobinuria (PNH), but it seems prudent to initiate thromboprophylaxis when pregnancy is documented.[54]

Low-molecular-weight heparin is considered optimal compared to unfractionated heparin, conferring less risk of heparin-induced thrombocytopoenia.

Primary options

enoxaparin: see local specialist protocol for dosing guidelines

OR

dalteparin: see local specialist protocol for dosing guidelines

Secondary options

heparin: see local specialist protocol for dosing guidelines

ONGOING

following acute clinical PNH with thrombosis: non-pregnant

1st line – lifetime anticoagulation

Back
ONGOING
|
following acute clinical PNH with thrombosis: non-pregnant
1st line – 

lifetime anticoagulation

Thrombolytic agents used in the acute stage of thrombosis should be followed by full anticoagulation with warfarin or heparin (preferably low-molecular-weight heparin).

Patients with documented thrombosis should receive lifelong secondary prophylaxis although, for patients on complement C5 inhibitor treatment, there is no clear evidence for the benefit of lifelong anticoagulation. Eculizumab has been shown to markedly reduce the incidence of thrombosis in paroxysmal nocturnal haemoglobinuria (PNH).

Most authors suggest a target international normalised ratio of 2.0 to 2.5.

Prophylactic anticoagulation with warfarin or heparin derivatives has been used with variable success.[51]

Primary options

enoxaparin: see local specialist protocol for dosing guidelines

OR

dalteparin: see local specialist protocol for dosing guidelines

OR

heparin: see local specialist protocol for dosing guidelines

OR

warfarin: see local specialist protocol for dosing guidelines

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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